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The term alcohol-drug interaction refers to the possibility that alcohol may alter the intensity of the pharmacological effect of a drug, so that the overall actions of the combination of alcohol plus drug are additive, potentiated, or antagonistic. Such interactions can be divided into two broad categories PHARMACOKINETIC and Pharmacodynamic. Pharmacokinetics are concerned with the extent and rate of absorption of the drugs, their distribution within the body, binding to tis There are a number of factors other than the drugs themselves that influence the speed and intensity of alcohol drug interactions in the human body. These include the patient's sex, weight, age, and race the presence or absence of food in the stomach and history of alcohol intake. For example, the levels of alcohol dehydrogenase (ADH), a stomach enzyme that oxidizes alcohol to acetalde-hyde, are lower in women than in men lower in Asians than in Western Caucasians and lower in alcoholics than in nonalcoholics....
Alcohol-drug interactions are complex. The consequences of using alcohol and drugs together vary with the dosage of the drug the amount of alcohol consumed the mode of administering the drug (oral, intravenous, intramuscular, etc.) and the nature of the drug (anticonvulsant, vasodilator, analgesic, etc.). The alcohol may alter the effects of the drug the drug may change the effects of alcohol or both may occur. Alcohol-drug interactions are most important with drugs that have a steep DOSE-RESPONSE CURVE and a small therapeutic ratio so that small quantitative changes at the target site of action lead to significant changes in drug action. In alcoholics, changes in susceptibility to drugs are due to changes in their rates of metabolism (pharmacokinetics) and the adaptive and synergistic effects on their organs, such as the central nervous system (pharmacodynamics). The clinical interactions of alcohol and drugs often appear paradoxical Sensitivity to many drugs, especially sedatives...
While adverse drug reactions are relatively rare for individuals taking St. John's wort extracts alone, interactions with other drugs are more commonly reported, and should be a source of concern for those taking St. John's wort along with other medications. Greeson et al. (9) and Barnes et al. (10) provide excellent reviews of drug interactions. The herb in some cases can increase the effectiveness of other compounds when taken together. This increase may be helpful to the individual or may increase the reaction of the compound to the point of toxicity. Conversely, the herb may decrease or even cancel the effectiveness of another compound (100). St. John's wort extracts may lead to an increase in hair loss when taken in conjunction with other tricyclic antidepressants as well as selective SSRIs (38). Microscopic examination of patients showing hair loss revealed a mixed telogen and normal anagen morphology that suggests drug interaction (100).
There are reports of baical flavonoids interacting with P450 enzymes. Baical flavonoids inhibit hepatic CYP1A2 (Kim etal 2002) and CYP2E1 expression (Jang etal 2003). Theoretically, inhibition of CYP1A2 and CYP2E1 may affect certain medical drugs metabolised by these P450 enzymes. There are, however, no clinical reports of such herb-drug interactions.
It is reported that 20-25 of drugs used clinically are metabolized by CYP450 2D6 3 . Consequently, many organizations screen candidate drugs for CP450 susceptibility, rejecting those that are substrates, because of absorption and drug interaction complications. This raises the barrier to selection and progression. Other features that contribute to absorption, disposition, and activity (such as lipophilicity and basicity) may also render them CYP substrates 4 . Thus it may be difficult, if not impossible in many cases to design out CYP450-susceptibility without compromising other desirable features of promising drug candidates. Formulation strategies to mitigate CYP450 liability and provide more consistent absorption may be worth considering in cases where drug candidates have novel and exciting possibilities as therapeutic agents.
Traditional models of general medical and behavioral health clinician interaction are typified by professionals with expertise in their respective disciplines (general or specialty medical versus behavioral health) using the services of those outside their discipline to address the medical or behavioral health issues for which they do not have extended training, largely on a referral basis. Once a consultation is obtained, either medical to behavioral or behavioral to medical, communication between consultant and consultee occurs only if obvious difficulties arise (eg, an adverse event, a drug-drug interaction). Further, there often is a perception that the diagnosis and treatment, particularly of behavioral health disorders, should be protected from other clinicians who are involved in the treatment of the same patient, because topics that are addressed in behavioral health are too sensitive for fellow medical professionals to maintain confidentiality. Because the interaction of...
Influenced by, among other factors circadian rhythms. Varying drug concentrations in the biosystem may be more effective if coinciding with and being capable of managing peak manifestations of the clinical condition. This is the case with anti-inflammatory conditions and antiasthma therapy among others 4 . Pulse, rather than persistent delivery may also alleviate or eliminate side effects 5 . Targeting a specific rhythm of a disease could reduce dosage, thereby reducing drug exposure and unwanted effects. Targeting rhythms may also prevent drug interactions, providing wider treatment options for patients suffering from multiple ailments.
In most countries where industrial hemp is licensed for cultivation, plants must not exceed a level of 0.3 THC, the principal psychoactive constituent of the species (Small & Marcus, 2003). Generally, the THC content of hempseed and hemp food is so low that psychotropic or even pharmacological effects can be excluded with certainty, even if larger quantities of food are consumed. THC limits for food have only been adopted in Switzerland since THC-containing food resulted in side effects for some consumers (Grotenhermen et al., 2009). Canada legislated THC limits for raw and semi-finished hemp products in 1998. THC limits for food are listed in Table 74.3. CBD, the main compound in industrial hemp, has been shown to have sleep-inducing properties (Small & Marcus, 2003). Dietary hempseed has been associated with platelet inhibition (Prociuk et al., 2008), so there is a possibility that bleeding times would be longer. This effect would be a significant concern in those patients under...
It has been estimated that approximately 1 In 30,000 people using SJW will experience an adverse reaction, including those attributed to drug interactions (Schulz 2006). The incidence of side-effects to SJW is approximately 10-fold lower than for conventional antidepressants (SSRIs). According to an overview of 16 postmarketing surveillance studies, gastrointestinal symptoms, sensitivity to light and other skin conditions and agitation were the most commonly reported side-effects and were generally described as mild (Linde & Knuppel 2005). PHOTOSENSITIVITY (UNLIKELYAT THERAPEUTIC DOSES) The most common adverse event among spontaneous reports is photosensitivity, which is estimated to occur in 1 in 300,000 treated cases. This can occur with a dose of 5-10 mg day hypericin, which is 2-4-fold higher than the recommended dose. Commission E has noted the possibility of photosensitivity reactions, particularly in fair-skinned people.
Application from aqueous systems needs to take account of drug stability, viz., potential for hydrolytic degradation. However, propensity for hydrolysis may not mean that degradation is an issue, since contact time with water during coating is limited and only happens until the surface is sealed. Prudent process design and appropriate process controls may obviate hydrolysis enabling aqueous coating. Drug interactions with nonaqueous solvents or residues therein also need to be considered during process design.
POPs can be made less effective by some commonly prescribed drugs that speed up liver activity, which may lead to breakthrough bleeding or even pregnancy, although this occurs rarely. Drugs that may affect the performance of the minipill include prescription headache pills containing barbiturates such as butalbital (Fiorinal, Fioricet, Esgic), the tuberculosis antibiotic rifampin, the oral antifungal drug griseofulvin (Fulvicin, Grifulvin, Grisactin), and antiseizure drugs containing carbamazepine (Tegretol), phenytoin (Dilantin), primidone (Mysoline), or phenobarbital. If you take such medications regularly, progestin-only pills are not recommended. New antiseizure drugs like Neurontin and Lamictal may be less likely to interact with birth control pills.
The prescribing of safe and effective drug therapy is becoming increasingly complex. More and more patients are receiving multiple drug therapies for acute and chronic conditions or diseases. As the number of medications taken by the individual patient increases, so does the potential for drug-drug interactions that have clinically important consequences. Because of the increasing concern about drug interactions, both the pharmaceutical industry and regulatory agencies have issued guidance papers on the conduct of in vitro and in vivo pharmacokinetic drug interaction studies 1 . In addition, labeling within various sections of the product package insert describes clinically significant drug interactions as well as relevant information about metabolic pathways of a drug. Recent regulatory actions by the US Food and Drug Administration (FDA) remind us of the potential risk for important drug interactions with anti-infective agents. In the early 1990s, patients experienced serious...
(270), azithromycin (271), terfenadine (272), and montelukast (data on file, Merck Pharmaceuticals) have been specifically studied and have no effect on theophylline clearance, nor is there evidence that other related medications have drug interactions with theophylline. On the other hand, while the quinolone antibiotics ofloxacin (273,274), norfloxacin (275,276), lomefloxa-cin (277-281), and flosequinan (282) have little or no effect on theophylline clearance, ciprofloxacin, enoxacin, and perfloxacin do slow theophylline elimination. Similarly, the H2 blockers famotidine (283), ranitidine (284), and nizatidine (285) have no effect on theophylline clearance, while cimeti-dine, uniquely in that class, can substantially slow theophylline clearance. Controlled clinical studies have demonstrated little or no effect of corticosteroids on theophylline elimination (286,287). Several drugs that do have some effect on theophylline clearance (288,289) cause sufficiently small effect to be of...
Blumenthal M et al. The ABC Clinical Guide to Herbs. Texas American Botanical Council, 2003. Bratman S, Kroll D. Natural Health Bible. Rocklin, CA Prima Health, 2000. Braunwald E et al. Harrison's Principles of Internal Medicine. New York McGraw Hill, 2003. Brinker F. Herb Contraindications and Drug Interactions, 2nd edn. Portland Eclectic Medical Publications, 1999.
There are various medical conditions and drug interactions that can increase the requirement for niacin. Examples are Hartnup disease, in which tryp-tophan transport in the intestine and kidney is impaired carcinoid syndrome, in which tryptophan turnover is increased and isoniazid treatment, which causes B6 depletion and hence interference with nia-cin formation from tryptophan. Hartnup disease (the name of the first patient being Hartnup) is a rare genetic disease in which the conversion of tryptophan to niacin is reduced, partly as a result of impaired tryptophan absorption. Affected subjects exhibit the classical skin and neurological lesions of pellagra, which can be alleviated by prolonged treatment with niacin. Another genetic disease which may respond to niacin supplements is Fredrikson type I familial hypercholesterolemia nicotinic acid is effective in reducing the raised blood cholesterol levels associated with this abnormality.
See AIDS HIV Adverse reactions. See also Herb-drug interactions definition, 105 herb-drug interactions, 105 St. John's Wort, 106 statistics, 106 Advertising Herb-drug interactions. See also Adverse reactions information for patients, 124 information for pharmacists, 107, 116 Pharmacists. See also Adverse reactions Herb-drug interactions American Society of Health-System
Little more than anecdotal evidence exists regarding interactions between pharmaceutical and herbal medicines. Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. However, studies on the common herbs indicate that significant herb-drug interactions exists. Thus St. John's wort (Hypericumperforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon, and theophylline furthermore, it causes intermenstrual bleeding, delirium, or mild serotonin syndrome, respectively, when used concomitantly with oral
Guide for Separating Food Folklore Facts from Fiction in Clinical Situations and A Practical Example
In the late 1980s, in a study examining the interaction between alcohol and felodopine (a calcium antagonist used to lower blood pressure), it was accidentally discovered that grapefruit juice, which was being used as a placebo, dramatically altered the drug's metabolism. The drug was a common one, the juice dose - about 6 ounces (180 ml) - was within the range many people drink, and the effects were large (similar to a doubling of the drug dose). Therefore, it was of potential clinical importance. Since then, more than 200 scientific papers have been published in peer-reviewed journals on the issue of drug interactions with grapefruit, confirming the original observations. By the mid-1990s, the finding had received a great deal of media coverage and the notion that grapefruit juice was dangerous for those on prescription drugs had become a subject of food folklore. This particular bit of folklore is an example of a strongly held belief for which there is some scientific evidence....
Recent concerns have been raised over herb-drug interactions with use of St. John's wort. Rare cases of serotonin syndrome have been reported with the combination of St. John's wort and selective serotonin reuptake inhibitors (66). Additionally, St. John's wort has been found to induce enzymatic Table 1 Potential Herb-Drug Interactions Due to St. John's Wort Table 1 Potential Herb-Drug Interactions Due to St. John's Wort Source Adapted from Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P. St. John's wort (Hypericum perforatum) drug interactions and clinical outcomes. Br J Clin Pharmacol 2002 54 349-356. Source Adapted from Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P. St. John's wort (Hypericum perforatum) drug interactions and clinical outcomes. Br J Clin Pharmacol 2002 54 349-356.
Some drug interactions have been investigated by in vitro and in vivo experiments, but results obtained have been inconsistent. St. John's wort, an herb commonly used in Western societies, was shown to suppress monoamine oxides in vitro, but such observations were absent in in vivo studies. Hence there is insufficient evidence of the antioxidant activity of St. John's wort causing hypertensive crisis. However, recently it was reported in Switzerland that St. John's wort may interact with other drugs e.g., the simultaneous administration of St. John's wort with digoxin, amitriptyline, or theophylline may reduce the effectiveness of the three drugs. Two patients with heart transplants were given St. John's wort when they were receiving their cyclo-sporin treatment. In 3 weeks' time, both had severe rejections. When the patients discontinued the herbal drug, the cyclosporin blood concentrations increased (27).
Black cohosh has been associated with mild gastrointestinal side effects that may be self-limited (8). Overdose can lead to dizziness, tremors, headaches, nausea, and vomiting. One case report of nocturnal seizures occurring in a woman who took black cohosh, primrose oil, and chaste tree exists (9). One case of fulminant hepatic failure after 1 week of therapy with black cohosh alone has also been reported (10). No clinically significant drug interactions are known.
Few drug interactions have been reported with amantadine. Ethanol in combination with amantadine can increase central nervous system (CNS) side effects, such as dizziness, confusion, and orthostatic hypotension (13). Antimuscarinics and medication with significant anticholinergic activity may increase the anticholinergic side effects of amantadine (13). A potential interaction of amantadine with bupropion has been reported (13,14). Affected patients develop restlessness, agitation, gait disturbance, and dizziness, and may require hospitalization depending upon severity. There is also a case report, suggesting amantadine toxicity from an interaction with hydrochlorothiazide-triamterene (15).
Classically, records are available in old Chinese medicinal literature on combined effects of herbs, their facilitatory and antagonistic effects. Today, not only drug interactions between herbs are important, but possible interactions between herbs and commonly used pharmaceutical preparations are becoming issues of great concern since users of herbal preparations are greatly increasing.
The increased use of herbal preparations is causing concern among doctors and pharmacists due to the widespread misconception among the American public that because herbal remedies are natural, they are free from the adverse effects or reactions associated with conventional drugs. Adverse effects, adverse reactions, and drug interactions are all areas of concern. An adverse effect is a ny unintended effect of a pharmaceutical product occurring at doses normally used in man which is related to the pharmacological properties of the drug, while an adverse reaction, is a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. 1 The manufacturers of herbal products are currently not required to submit proof of safety and efficacy to the FDA before bringing a product to market. For this reason, the adverse effects and drug interactions...
No health hazards or side effects known with proper therapeutic dosages (PH2). None known (WAM) Commission E reports no contraindications or drug interactions for the fruit. Occasional mild laxative effects are reported (AEH). The long term safety and the advisability of the use of these extracts in pregnant or women of potential childbearing remain to be established (LRNP, March 1988). One observational study (n 2000) reported circa 1 side effects, mostly transient GI distress (SHT). May be used by pregnant and lactating women (SKY). Antagonizes phentolamine and yohimbine (PH2). One Australian report, attributed to something other than silybin in the milk thistle product, suggested abdominal cramping, diaphoresis, diarrhea, nausea, vomiting, and weakness (PH2). Silymarin may induce p450. Milk thistle decreased the trough concentrations of indinavir in humans (X15916450).
Stereoselectivity in plasma protein binding may also influence drug clearance for compounds with a low extraction ratio as total clearance is proportional to fraction unbound. In addition stereoselective displacement of drug enantiomers from plasma protein binding sites may give rise to complexities in drug interactions (see Section 4.6.3). Interactions between enantiomers for plasma protein binding sites may also result in pharmacokinetic complications. For example the protein binding of disopyramide is stereoselective and concentration dependent and the pharmacokinetic parameters of the individual enantiomers differ depending if the drug is administered as the racemate or single isomer.
In contrast, alcohol consumed on a regular basis brings on the manufacture of enzymes in the body, leading in turn to accelerated metabolism and increased clearance of some drugs, including blood-thinners, oral diabetic medicine, and medicine prescribed against convulsions. Thus, these therapeutic drugs can become less effective, so the patient needs closer monitoring. Alcohol-drug interactions do not generally result directly in death. However, there is evidence for a contributory role of alcohol in drug-related fatalities, for example, in car accidents. Anyone who drinks even moderately should ask a physician or pharmacist about possible alcohol-drug interactions. Adapted from MA. Rizack & C.D.M. Hillman (1987), Adverse interactions of drugs. In The Medical Letter handbook of adverse drug interactions. New York Medical Letter.
There are very few well-designed studies and consequently very little evidence to support or refute the use of most complementary therapies for the treatment of PD. This does not mean that alternative therapies cannot help someone with PD, but for Western-trained healthcare providers treating someone with PD who is considering alternative therapies, it is difficult to know what and how to advise them. The first rule in medicine is do no harm, so if a particular therapy such as massage therapy is not thought to be harmful then it might be recommended. On the other hand, ingesting an herb, injecting glutathione, or ingesting a homeopathic remedy without any proof that it is beneficial and without knowing the potential harmful effects or drug interactions may not be in the best interest of a person with PD. Specific complementary therapies that are commonly prescribed by alternative practitioners are reviewed in the following section. As the majority of these therapies, especially those...
Overall, based on clinical experience and the available scientific data, SSRIs and TCAs may be considered useful for the treatment of depression in PD, and the agent that provides the best overall clinical benefit-to-risk profile should be selected (168). Amoxapine and lithium should be avoided, given the propensity of these agents to worsen motor symptoms and the availability of safer agents (169,170). Additionally, the nonselective MAO inhibitors (e.g., isocarboxazid, phenelzine, and tranylcypromine) should be avoided in levodopa-treated patients due to the risk of hypertensive crisis. Several antidepressants, such as bupropion, fluoxetine, fluvoxamine, nefa-zodone, and paroxetine, are potent in vivo inhibitors of various cytochrome P450 (CYP450) drug-metabolizing isoenzymes (171,172). These antidepressants may increase the risk for drug interactions.
Ingestion of cranberry is generally considered quite safe. Some concern over the potential for development of nephrolithiasis exists due to increases in urinary oxalate with regular consumption (23). The clinical significance of this finding is unclear. No significant drug interactions have been documented to date.
Frequently available to people undergoing cancer treatment. Be aware that neither of these treatments should cause pain. If they do, either the person performing the treatment is not skilled enough, or the person receiving the treatment is hypersensitive and this form of therapy is not a good option for him or her. Mind-body therapies (for example meditation and hypnosis) are also often available in cancer centers. If you are considering taking dietary supplements or botanicals for any reason, including pain relief, talk to your doctor about possible side effects and drug interactions.
Tem, echinacea is not recommended for patients with autoimmune disease or HIV for fear of worsening the disease. This concern remains a theoretical risk rather than an established fact. No long-term data on the safety of chronic use are available at present. No significant drug interactions have yet been identified.
Early case reports suggested the efficacy of oral verapamil in mania. This led to several further trials. It appeared that there was a great deal of potential for an inexpensive, well-tolerated agent, which had been well tested in the field of cardiovascular medicine, had few drug-drug interactions, no need for serum level monitoring and low teratogenicity compared to existing options.
Numerous controlled and uncontrolled treatment trials provide support that outcomes in those who receive evidence-based treatment for most common mental illnesses, such as depression 61 , are as good as or better than those for many common chronic general medical illnesses 62 , such as diabetes 63 , congestive heart failure 64 , or arthritis 65 . Furthermore, recent evidence suggests that clinical outcomes in nonmedically ill patients can be generalized to psychiatric illness that is seen in those with medical comorbid-ity, although special attention is required in applying specific interventions because medical illness-based differences in treatment response, drug interactions, and adverse events that are related to treatment can occur 3,66 .
Drug interactions can generally be classified as either pharmacokinetic or pharmacodynamic. Pharmacokinetic interactions result from processes that lead to a change in the disposition of one or more drugs and result in a change in clinical response. The most common form of a pharmacokinetic interaction occurs when one drug induces or inhibits the metabolism and or elimination of another, and the steady-state concentration of a drug is lowered or raised. Alcohol can affect many medications through competition for the same microsomal oxidase system, involved in the metabolism of various drugs 22 , Pharmacodynamic interactions result when drugs have separate actions that are either augmented or antagonized when the drugs are used together. Alcohol appears to enhance aspirin-induced gastric mucosal damage and aspirin-induced prolongation of the bleeding time. Alcohol-drug interaction varies greatly in the range between social drinkers and heavy chronic drinkers. This phenomenon is also...
At physiological pH both cromolyn and nedocromil are small, water-soluble, highly ionized compounds with negligible fat solubility that are poorly absorbed from the gastrointestinal (GI) tract (8). These properties are responsible for the inability of these drugs to enter the intracellular space of cells leading to their excretion in the urine (80 ) and feces after biliary secretion (20 ) (8). CS binding to plasma proteins is poor and reversible, which accounts for the extremely low incidence of adverse drug interactions (7). Less than 1 of an oral dose of CS is absorbed from the gastrointestinal tract, but approximately 7 to 9 of an inhaled dose reaches the systemic circulation with peak plasma levels achieved 10 to 15 minutes after inhalation (9). Relatively rapid clearance occurs from the lung with up to 75 of the inhaled dose being removed by two hours. Only 2 of the inhaled dose may remain in the lung for 24 hours (7-9). Plasma half-life is less than two hours and is nearly...
She rang me immediately after this session to report how pleased she was with his progress. She felt his anxiety levels had dropped dramatically and she did not feel he needed any medication, such as anti-depressants, at this time. I was very relieved, as we wanted to avoid any drug interaction for my son, if at all possible.
The benzodiazepines supplanted the barbiturates because they seemed to be at least as effective, with few side effects and less likelihood of producing addiction. Benzodiazepines are preferred to placebo by drug abusers but vary in this regard for example, diazepam (Valium) and lorazepam (Ativan) seem more likely to be taken than is oxazepam (Serax or Serehid). Benzodiazepines have been abused in various countries at various times. They have been injected as the main drug of abuse or as part of a polydrug-abuse pattern. Abusers of alcohol may also abuse benzodiazepines, finding that with drug interaction a potentiation occurs, that is, the combination is particularly powerful. Most benzodiazepine abuse is with drugs obtained legally from a number of complaisant pre-scribers, but the very heavy user may have to resort to illicit sources of supply. About 50 percent of abusers of benzodiazepines were introduced to the drug within the medical context.
While numerous clinical guidelines suggest that treatment of BD in the elderly should be different from younger populations, there are actually no randomized controlled treatment trials in elderly bipolars to ground these recommendations in an evidence-based approach 146-148 . Unfortunately, well-documented age-related changes in pharmacokinetics and pharmacodynamics, which will be reviewed next, make the adoption of treatment recommendations from studies of middle-aged patients hazardous. Furthermore, the elderly frequently suffer from chronic medical illnesses and are being treated with numerous concomitant medications which make the risk of adverse drug reactions and drug interactions much greater.
The elderly may be more susceptible than younger populations to lithium-induced side effects, such as delirium 151, 152 , prolonged neurotoxicity 160 , and increased lithium-induced hypothyroidism 150 . Toxicity may also be caused by drug interactions. For example, drugs such as thiazide diuretics, angiotensin converting enzyme inhibitors and indomethacin can all lead to increases of serum lithium and possible tox-icity.
The lack of research on the efficacy of pharmacological and psychological interventions for the treatment of depression associated with pain in cancer survivors is problematic. Questions concerning the relative efficacy of depression-specific interventions for cancer survivors with persistent pain need to be addressed in order to guide treatment decisions. In addition, there is little or no information available about the influence of drug interactions, particularly opioids, on the efficacy of depression-specific interventions for depressed cancer survivors with persistent pain. Given that persistent pain and depression are both associated with activity withdrawal (in other pain conditions), the depressed cancer survivor with persistent pain may benefit most from multidisciplinary approaches that combine pharmacotherapy, depression management strategies, and activity mobilization strategies.83
Cardiovascular risk factors, such as hypertension, diabetes, and hyperlipidemia, as well as cardiovascular disease states, such as coronary heart disease, heart failure, and certain arrhythmias, are amenable to a variety of therapeutic interventions that have been proven to be beneficial. However, the combination ofthese interventions has rarely been studied in a rigorous scientific way. No data are available that analyze the relevant contribution of each drug to the overall outcome in a given patient. Progress has been made in identifying and understanding some drug interactions, allowing the rational combination of certain drugs in a given patient. Drug combinations may be rational for several reasons (Figure 10)
The therapeutic benefit from theophylline has required consideration for its use in a manner that minimizes its potential for adverse effects (90). Drug interactions or alterations in clearance for other reasons have the potential to cause toxicity. However, toxicity has occurred most commonly from errors in dosage (91,92). Fortunately, most cases of toxicity are mild and readily reversible without residual effects. In virtually every case where there has been serious toxicity such as seizures with neurological damage, serious errors in dosage occurred, often compounded by other factors such as drug interactions or failing to be alert for early signs of toxicity such as nausea, vomiting, central nervous stimulation, or tachycardia.
Drug interactions have not been documented with cromolyn. Overall, cromolyn can be used safely in elderly patients with hypertension, heart disease, seizure disorders, or prostate disease. Cromolyn is classified as category B in pregnancy. Patients who will benefit from intranasal cromolyn include children 2 years, elderly patients, patients with comorbidities, patients reluctant to take medications, patients and athletes who undergo drug monitoring to avoid corticosteroids (3).
Significant interindividual variability exists in the outcomes of drug interactions. This variability is associated with patient-specific factors such as disease state, other concomitant medications, and genetics. Specifically, there is at least 10-fold interindividual variability in CYP450 content, which is most likely due to a combination of clinical factors and genetics. In addition, certain CYP450 enzymes (eg, CYP2D6, CYP2C9, CYP2C19) exhibit clinically important polymorphisms that contribute to ethnic differences in metabolism as well as drug safety and efficacy. Thus, each interaction in each individual patient must be assessed for clinical relevance. In addition to pharmacokinetic drug interactions, pharmacodynamic drug interactions may occur. Pharmacodynamic drug interactions are associated with a change in efficacy or safety of the object drug, with or without a change in its pharmacokinetics. Examples of this type of interactions include the additive risk for developing...
When a patient does not respond to a specific antidepressant after a trial of 2 to 4 weeks, the physician may prescribe another medication. If the new drug is from the same group as the first antidepressant, the physician can rapidly decrease the dosage of the first drug while increasing the dosage of the second. If, however, the new antidepressant is from a different category, a ''washout time'' must be allowed in order to prevent drug interactions. A washout period of 2 to 3 weeks is necessary when the patient is switched from an MAO inhibitor to a tricyclic a period of 4 to 5 weeks is necessary when switching from an SSRI to an MAO inhibitor.
At normal therapeutic dose levels warfarin is a relatively safe drug and cases of excessive dosage may be managed by the administration of vitamin K. The major problems associated with the use of warfarin arise as a result of drug interactions and warfarin is probably the most extensively investigated drug with respect to stereoselectivity and drug interactions. Some agents selectively interact with (S)-warfarin, e.g. phenylbutazone, sulfinpyrazone, whereas others are selective for (R)-warfarin, e.g. cimetidine, enoxacin, and other agents, e.g. amiodarone show no stereoselectivity. The majority of the interactions
Drug interactions are not a prominent problem with entacapone, although the capability of entacapone to chelate iron in the gastrointestinal tract has been noted (70), and it has been suggested that an interval of two to three hours be allowed between entacapone and iron ingestion (18). Although animal studies have suggested that COMT inhibition may increase apomorphine bioavailability (71), such an effect has not been demonstrated in humans, even when administering a double dose of 400 mg entacapone (72).
Many alcohol-drug interactions occur at the level of actual metabolism. Ethanol (ethyl alcohol common in wines and liquors) will compete with such other alcohols as METHANOL (methyl alcohol called wood alcohol) or ethylene glycol (antifreeze), for oxidation via alcohol dehydroge-nase. In fact, treatment against poisoning by methanol or ethylene glycol involves the administration of ethanol as the competitive inhibitor or the addition of inhibitors of alcohol dehydrogenase such as pyrazole or 4-methylpyrazole.
Some thiol-bearing compounds in garlic and onion and their relatives can cause acantholysis in vitro (Brenner et al., 1995) and possibly pemphigus in vivo. More than 5 cloves a day may induce flatulence and heartburn (Castleman, 1996) and 'thin blood' (people taking blood thinners may overthin their blood thereby). Some people are very allergic to garlic. Contraindicated in hyperthyroid (TRA) Commission E reports rare GI disturbances, allergic reactions, and change of odor of skin and breath (Commission E). Allergic reactions of contact dermatosis and severe asthmatic attacks (from inhalation of garlic powder) may occur. Topical application of garlic or garlic oil may cause local irritating effects. Nausea, vomiting, and diarrhea may occur following ingestion of fresh garlic bulbs, extracts, or oil (AEH1). Sulfides may irritate the GI tract or cause dermatosis (CAN). Fresh garlic is reportedly dangerous to children (AHP). Use sparingly with children under 2 years...
The preponderance of clinical studies point toward St. John's wort as being relatively safe, especially at typical dosages. However, high dosages might lead to phototoxicity in susceptible individuals. Extracts of St. John's wort do appear to interact with other medications, especially owing to impact on liver enzyme function. Therefore, individuals taking St. John's wort along with other medications should be cognizant of such potential drug interactions.
Drug interactions with grapefruit juice serve as a good example of how an apparently innocuous dietary constituent can interact with potent drugs, which could result in serious toxicity. A number of Chinese herbal medicines are derived from citrus fruits such as chen pi (rind of Citrus reticulata) or zhi shi (unripe fruits of Citrus aurantium) and these could have similar effects although it has been suggested that the interaction is specific for grapefruit products and in vitro findings suggested the flavonoid, naringenin, or the furanocoumarin, 6',7'-dihydroxybergamottin, were the active components causing drug interactions (62). The serendipitous finding that grapefruit juice increased the oral bioavailability of felodipine and to a lesser extent nifedipine provided the instigation for a series of investigations to explore the mechanism of this effect (63). Lown and colleagues reported that grapefruit juice decreased small-bowel epithelial cell CYP3A4 concentration by 62 , but did...
Antibiotics have been an important part of the therapeutic armamentarium against infectious diseases for decades. Although most practitioners have a penchant for using newer antimicrobials, some older antibiotics remain highly effective and underused. The side effects and drug interactions of older antibiotics are well known. Importantly, older antibiotics are invariably less expensive than most newer preparations with comparable activity.
The principles of drug interactions can be used clinically for the treatment of acute INTOXICATION and for WITHDRAWAL by transforming, reducing, or blocking the pharmacological properties and or the toxic effects of drugs used and abused for nonmedical purposes. Although these interactions often involve a competition with the abused drug for similar central nervous system RECEPTOR sites, other mechanisms are also clinically relevant. Disulfiram and Alcohol (Ethanol). One such nonreceptor-mediated interaction involves DISULFIRAM (Antabuse) and ethanol (alcohol). Since an ethanol-receptor site has not yet been conclusively identified, specific receptor agonists and antagonists are not yet available for the treatment of ethanol intoxication, withdrawal, and abstinence (as they are for opioids). Disulfiram is sometimes used in the treatment of chronic ALCOHOLISM, although the drug does not cure alcoholism rather, it interacts with ethanol in such a way that it helps to strengthen an...