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Unwanted drug interactions

Drug interactions often have an unwanted effect. This may be to inhibit the effect of the drug (antagonism) or to cause toxicity due to potentiation or alteration in the rate of metabolism or excretion. Table 19.1 Definitions of drug interaction terminology Table 19.1 Definitions of drug interaction terminology

Drug Drug Interactions

Consideration of drug-drug interactions is essential in situations where multiple medications are used simultaneously to address co-occurring conditions. Safer et al. (2003) have reported a rising trend in the use of multiple, potentially interacting psycho-tropic medications to treat children and adolescents with psychiatric morbidities, whereas Robinson and Owen (2005) found the use of multiple medications to be a common cause of patient morbidity. Pharmacokinetic drug-drug interactions can influence drug concentrations through changes in absorption, distribution, metabolism, or excretion. Pharmacodynamic interactions can involve alterations in the pharmacological response to drugs that might occur through alterations in drug-receptor binding, receptor function, and signaling at the in-tracellular or intercellular levels. Both pharmacoki-netic and pharmacodynamic properties are likely to be developmentally dependent on changes in factors such as body composition, organ system...

Identification of Drug Interactions

Most pharmacokinetic drug-drug interactions involve the effect of a drug on the cytochrome P450-mediated metabolism of another agent (Sandson et al. 2005). For these interactions to have clinical importance, the drug needs to have a narrow therapeutic index and only one primary P450 enzyme involved in its metabolism. The metabolism of drugs that are substrates of multiple cytochrome P450 enzyme subfamilies is not usually altered to a clinically significant degree by the inhibition of one P450 enzyme because metabolism can proceed through the remaining unaffected metabolizing enzymes. lished medication regimen. Drugs with a narrow therapeutic index that are metabolized through a single P450 pathway are particularly vulnerable to such interactions. The addition or removal of drugs that inhibit or induce cytochrome P450 enzyme activity might require substrate dosage adjustments to maintain clinical efficacy and minimize potential toxic side effects. Clinical monitoring for signs of...

Drug Interactions Tolerance And Dependence Drug Interactions

It should be evident from the preceding discussions of processes studied in pharmacokinetics and pharmacodynamics that vast potential exists for one drug to affect the action of another, if they are both in the body at the same time. Drugs can alter absorption, distribution, biotransformation and excretion of other drugs. Furthermore, antagonistic, additive, and synergistic interactions can occur on the level of molecular targets of the drugs, or because of functional interactions in affected physiological systems. Interactions occur not only between prescribed psychoactive drugs but also with such socially accepted drugs as alcohol, nicotine, and caffeine, not to speak of illicit psychoactive drugs. Many drug interactions go unnoticed because of their minor significance to well-being and the inability of the subject to ascribe the symptoms to drug interaction. Others are potentially life-threatening, such as the additive effect of central nervous system (CNS) depressants, such as...

Herb Drug Interactions

An important concern for many clinicians is the possibility of herb-drug interactions. Fugh-Berman and Ernst (2001) compiled case reports and other data from three research databases and contacted 10 supplement manufacturers, ranking studies according to a 10-point scoring system, based on how clearly the report accounted for comorbidities and adequately described the circumstances surrounding the interactions. Of 108 reported interactions, 14 were classed as likely to exist, 20 were deemed possible, and 74 were classed as unevaluable. Many of the most likely herb-drug interactions involved St. John's wort, an herb used in the treatment of depression. This botanical affects the cyto-chrome P-450 3A4 system, potentially lowering the serum levels of several drugs, including oral contraceptives and cyclosporine (Brinker, 2001). Data from Twelve Supplements You Should Avoid. Consumer Reports, May 2004, p 15 Basch EM, Ulbricht CE. Natural Standard Herb and Supplement Handbook The Clinical...

Definitions and Terminology

In the US, the provision of medication in response to prescriber orders and the management of the supply of medicines is the role of pharmacy information systems.5 These systems are designed to manage information relating to the use of medicines in patient care and include functionality for online order entry, pharmacist review, medication profiles, label printing, stock or inventory control and reporting (medication use reports, dispensing reports etc.). Since some pharmacy information systems may be used to facilitate EP, with online order entry and, in some cases, clinical decision support tools, some commentators consider them as EP applications. However, this is in contrast to the UK, where there is a more clear demarcation between pharmacy systems, which are well developed and universally used, and EP systems, which are still in their infancy.

Clinical Pharmacology

Antibiotics, e.g., neomycin or other beta-glucuronidase inhibitors, such as cyclosporin A, which inhibits the cMOAT-mediated biliary excretion of SN-38 ( 78,79). Furthermore, cytochrome P-450 3A4 (CYP3A4) metabolizes irinotecan into several oxidized derivatives, including APC (7-ethyl-10- 4-N-5-aminopentanoic and NPC (71,80-83). The various genes with a putative role in irinotecan disposition are shown in Fig. 2. Both metabolites are also poor inhibitors of topoisomerase I and only the minor-metabolite NPC can be further converted to SN-38 (74,83,84). Because CYP3A4 is involved in the biotransformation of many other drugs, there is a potential risk of clinically relevant drug interactions. A Phase I study of irinotecan in malignant glioma patients revealed that the clearance of irinotecan was significantly faster in patients who required cotreatment with anticonvulsants and glucocorticoids - inducers of the CYP3A4 enzyme - as compared with patients who did not

Second and thirdgeneration calcium antagonists

Mibefradil is a tetralol derivative which selectively blocks T-type calcium channels and was recently introduced for the treatment of hypertension and angina. It causes coronary artery vasodilatation without suppressing myocardial contractility, and heart rate is decreased. Although generally well tolerated, mibefradil was associated with multiple drug interactions and has now been withdrawn from clinical use.

What Are The Goals Of Therapy

The strategy for designing and implementing a treatment plan begins with an accurate diagnosis of the patient's seizure type(s) and a measurement of seizure frequency and severity. Referral to a neurologist may be appropriate to establish the diagnosis and to formulate a treatment plan, but subsequent follow-up is often managed by the primary care physician. In evaluating the effectiveness of treatment, the clinician takes into consideration any side effects of the medication and any psychosocial problems the patient may be experiencing. The treatment process is more likely to be successful when the clinician has a working knowledge of available AEDs, AED pharmacokinetics, drug-drug interactions, and AED side effects.

Development of EP Systems in the United States

The most notable centre for EP use in the US is the Brigham and Women's Hospital, Boston.9-11 The Brigham and Women's CPOE functionality was developed in the early 1990s as part of an in-house information system, the Brigham Integrated Computing System, which was designed to manage all aspects of the hospital's administrative and clinical processes. The initial system included formulary prescribing menus, default doses or dose selection, display of relevant laboratory results and limited sensitivity checking, drug interaction checking and laboratory test interaction checking. Further checking functions were added in an upgrade to the system in 1996.

Pharmacologic Therapy

Antacids also have clinically significant drug interactions with ferrous sulfate, iso-niazid, sulfonylureas, and quinolone antibiotics. Antacid-drug interactions are influenced by antacid composition, dose, dosage schedule, and formulation. Because all H2RAs have similar efficacy, selection of the specific agent should be based on factors such as differences in dosage regimen, safety profile, and cost. In general, H2RAs are well tolerated. Patients should be monitored for adverse effects and potential drug interactions. Cimetidine may inhibit the metabolism of certain medications such as theophylline, warfarin, or phenytoin. An alternate H2RA should be selected if the patient is taking any of these medications.

Development of EP Systems A European Perspective

Nielsen and Dybwik33 have described the use of decision support software in Norway to alert intensive care unit clinicians to drug interactions. They used the internet-based decision support system, DRUID ( to evaluate drug interactions of drugs prescribed for patients during the first 24 h of their intensive care stay. Using the system, they identified 274 potential drug interactions in 110 patients. However, while just over half of the interactions required extra precautions to be taken (e.g. dose reduction), there were very few serious interactions noted.

Recommended References

Proponents and critics of herbal remedies alike recommend books by herb expert and professor of pharmacognosy, Dr. Varro Tyler The Honest Herbal A Sensible Guide to the Use of Herbs and Related Remedies and Herbs of Choice The Therapeutic Use of Phytomedicinals (both from Pharmaceutical Products Press, an imprint of Haworth Press, Binghamton, N.Y., 1993 and 1994). More related to cancer, see Barrie R. Cassileth, K. Simon Yeung and Jyothirmai Gubili Herb-Drug Interactions in Oncology, Second Edition (PMPH-USA, 2010).

Prevention and Treatment

The treatment of HIV is covered in Chapter 17. However, there are specific opportunities for preventing pulmonary OIs in HIV-infected patients. Antiretroviral therapy (ART) has transformed HIV AIDS into a chronic disease in which CD4+ counts can often be maintained above levels at which OIs are likely. For preventing pulmonary complications, prophylaxis regimens that were effective in decreasing OI rates in the pre-ART era still play a role in the care of patients with more advanced disease. ART has resulted in dramatic decreases in HIV-related mortality and OIs, but specific challenges are raised by the cost and complexity of the drug regimens as well as drug-drug interactions, particularly when mixing prophylactic antibiotics or antituberculous agents with protease inhibitors.

Clinical application

Medical contraindications include severe systemic disease, particularly respiratory disease such as severe chronic obstructive airways disease, and severe mental or physical special needs. A number of drug interactions contraindicate the use of intravenous benzodiazepines, particularly if a patient has a history of psychiatric treatment or has been prescribed benzodiazepines over a long period of time, thereby making the patient very tolerant to the drug. Intravenous sedation should be avoided wherever possible in patients who are either pregnant or breast-feeding.

Reduction of Medication Errors Due To the Availability of Electronic Decision Support Tools At the Point of Prescribing

(b) Drug interactions The key issue with proactive DS functions is that they must be sufficiently comprehensive to be of clinical value, but designed in such a way that they are not intrusive to the clinical user, which might lead to important warnings being disregarded by the user. This is a delicate balance and requires considerable thought if the rules are going to be configured within the EP application - for this reason, some implementers have chosen not to support DS functions at all, rather than implement them in a partial manner or without full evaluation this is the reason why the EP project at Southmead Hospital, Bristol, did not implement any DS functions.20 In the past, for example, there have been some systems that have limited the number of drug interaction warnings to two or three per drug, or limited the number of allergens for sensitivity checking to two per patient. Limitations of this nature are clearly not acceptable if an EP system is to provide comprehensive DS...

The use of interactions to treat patients

Sometimes, a known drug interaction is deliberately employed as it has therapeutic value. A well-known example of this is giving oral drugs with certain types of food to enhance absorption, e.g. giving griseofulvin tablets with corn oil or cheese. Two drugs with a different action can be given together to increase the therapeutic response - this is known as synergism (Table 19.1). If the response is the same as the sum of the two individual drugs, the effect is known as summation. However, in some cases, the response is greater than the sum of the two individual drugs. This effect is known as potentiation. Another therapeutic interaction is when the rate of metabolism or excretion from the body is altered to prolong the therapeutic effect, or conversely to increase clearance rate.

The effect of toxins on the body

All organs in the body are susceptible to toxins. However, because of their role in drug metabolism and excretion, the liver and kidney are most at risk from damage. The mechanisms of action vary but include interfering with cellular function, alteration or destruction of vital enzymes, or competing for receptor sites, preventing the endogenous ligand from binding. Drug interactions can cause toxicity in this way, increasing the plasma concentration levels of the drug with less affinity for the binding site.

Data Support for Electronic Medicines Management

For example, medicine name, form, strength, route of administration, synonyms, dose, storage conditions, etc. This basic dataset would be required for each prescribed item for a patient. In addition to this indicative information, it is expected that EP systems would provide referential information on prescribed medicines - for example, standard information on contraindications, precautions, side-effects and drug interactions. The accuracy and validation of these data are essential, and issues relating to the implementation of drug data will be discussed at length in this chapter. Some EP systems use their own drug databases, produced in-house from previous implementations others will use a drug database supplied by a third party data supplier. The source of the drug data has various implications which will be discussed in some detail later in the chapter. 4. Decision support (DS) warnings. In addition to the data items described in the first three categories above, which...

The Development of Medicines Information Reference Sources

The primary literature consists of clinical trial reports, reviews of specific therapeutic issues, case studies and anecdotal reports. The secondary literature consists of drug information compiled from primary sources. This might include recognised reference books, addressing specific clinical issues, such as Stockley's Drug Interactions , or Briggs' Drugs In Pregnancy . The secondary literature also comprises of recognised pharmaceutical compendia. A compendium is a book, with a section or monograph, on each listed medicinal product or drug substance. Some of the compendia provide standards for manufacturing and quality control purposes (for example, the British Pharmacopeia and the European Pharmacopeia) and are of little value for prescribers and clinical professionals. Others contain more evaluated clinical information (for example, the Martindale Extra Pharmacopeia) or provide treatment guidelines for rapid reference (for example, the British National Formulary (BNF) or the...

Data for Decision Support Tools

In addition to the drug database, third party data suppliers will often provide data and messaging for clinical decision support (DS) functions. Typically, these will include sensitivities, drug interactions, drug-disease interactions, duplicate therapy warnings and precautions. When a medicine is prescribed for a patient, the EP system will query the other patient- and medicine-related data, and return any clinical warnings about the prescribing of that medicine, in relation to other medicines prescribed and other patient factors. The accuracy and reliability of clinical alerts is a key consideration in the implementation of DS tools. In the past, various implementers have chosen not to introduce any DS functions in their EP system at all, rather than set up a DS system that does not have an adequate data platform or appropriate granularity in the data.16 Another issue is that many DS tools on proprietary systems may display large numbers of warnings that may be of questionable...

Evidence Based Treatment Approaches

Pressant-treated adults have generated interest in the possibility that active psychiatric treatment might modify the disease course (Mikocka-Walus et al. 2006). The efficacy of SSRI antidepressant medications for major depression, obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders has been demonstrated in physically healthy children and adolescents (Bridge et al. 2007). There is little reason to suspect that the presence of IBD is a contraindication for the use of antidepressant medications in clinically appropriate circumstances, although appropriate caution must be exercised, particularly with regard to drug interactions.

Antidepressants in the selective serotonin reuptake inhibitor category SSRIs

The oral medications, first introduced in 1997, work by blocking an enzyme (phosphodiesterase type 5) in the penis, thereby allowing the smooth muscles to relax and the penis to fill with blood. They do not produce an erection by themselves, but only when accompanied by erotic stimulation. The effective dose varies among men some men, but not all, get a better response at a higher dose. These medications should never be taken by men who are also taking nitrates for angina or chest pain the drug interaction can be fatal.

EP Systems Support for Professional Practice

Systems to support ward-based clinical pharmacy activities and interventions. Marriott et al.2 undertook a study in the UK comparing the number and type of pharmacist interventions at Queens Hospital, Burton on Trent (BH), where a fully integrated patient data and prescribing management system has been implemented, as discussed previously and at Good Hope Hospital, Sutton Coldfield (GHH), where a traditional paper-based system was in place. Over a period of 2 months in 2003, a larger number of clinical interventions were made at BH - 2,512 interventions (equivalent to 0.2 interventions per finished consultant episode (FCE)) compared to 763 interventions (0.05 interventions per FCE) at GHH. Furthermore, the types of intervention were different between the two hospitals. Thirteen per cent of the pharmacist interventions at GHH, the paper-based hospital, were concerning drug interactions, use of non-formulary medicines, route changes and prescription legibility, but there were no...

EP Systems and Patient Centred Medicines Reviews

(d) Whether there are any significant drug interactions or drug sensitivities that may be giving rise to side effects (c) The system would then guide the reviewer through a structured review process. For each prescribed medicine on the profile, the system would advise the reviewer of any significant clinical checks (drug interactions, drug-disease interactions, sensitivities, duplicate therapies), and would direct the reviewer to

EP Systems Support for Continuing Professional Development

In addition to this, the active clinical decision support that an EP system provides (drug interactions, sensitivities, precautions and contraindications) is a potentially rich source of guidance to less experienced prescribers, as long as it is implemented in such a way that warnings are clear, relevant and do not excessively impede the prescribing workflow.

EP Systems A Gateway to Medicines Information Reference Sources

As discussed in Chapter 5, published sources of drug information have in the past consisted of the medical and pharmaceutical primary literature from hardcopy journal publications, together with secondary reference publications, such as recognised compendia - for example, the Martindale Extra Pharmacopeia (Martindale), and Stockley's Drug Interactions - and periodicals - for example, the British National Formulary (BNF), or the Monthly Index of Medical Specialities (MIMS). Now, however, many of the pharmaceutical compendia - for example, the BNF or Martindale - are available in electronic format, on CD-ROM for single-user or network access.

Predicting Which Patients are More Likely to Respond

Markers are probably the more fruitful. The key question from a clinical development perspective is if trials should be conducted in selected patient populations or in general groups. One factor to consider is the rationale behind the target-drug interaction. In situations such as bcr abl, c-kit or HER2 in which it was relatively clear that the agents would work in selected populations, the decision to base the development on such criteria was right (80, 81). For many other targeted agents, however, such knowledge is not available at the time studies commence or there are no well-validated tests to measure the target in tumor tissues. It is clear that more preclinical studies oriented to define biomarkers of response and not just activity is needed. In addition, in situations where a biomarker for patient selection is not available every effort should be made to collect tumor tissue for translational studies. Indeed, modern clinical trials should obligatorily make an effort to collect...

Psychosocial Adjustment

Delirium may occur in acute illness or be due to toxic drug interactions. Underlying medical causes such as medication intoxication should be evaluated. Certain antiretroviral agents such as efavirenz have been associated with a number of significant CNS effects including dizziness, sleep disturbances, and mood alterations that often resolve after the first few weeks of therapy but also may persist

Evidence Based Treatment

For treatment of depression in HIV-positive youth, current treatment guidelines for the management of depression in children can be followed. Antidepressants, including tricyclic antidepressants as well as SSRIs and bupropion, have been used empirically, and off label in many cases, in youth with HIV (Pao and Wiener 2008). There is no evidence that one SSRI is more effective than another in HIV-positive youth. Citalopram or mirtazapine is used due to fewer side effects and less problematic drug-drug interactions. Mirtazapine may be used to promote weight gain and treat insomnia. Methyl-phenidate, which may also potentiate opiate treatment, may be useful for pain and depression in HIV (Walling and Pfefferbaum 1990). Treatment options for bipolar disorder in HIVpositive youth include divalproex sodium when neutropenia is not a concern, other mood stabilizers such as lamotrigine, and, rarely, lithium (Kowatch and Delbello 2006). Similarly, drug-drug interactions, neutropenia, and...

Records Management and Multiuser Systems

Can be catered for by a small and well-defined set of prescriptions, perhaps available on the device as pre-defined orders (PDOs). (b) Because the portable device is not operating in real time, the synchronisation of the slave application with the main system is of particular significance in EP applications. If, at the point of synchronisation, a prescriber is already using the main system, then the data transfer from the portable device should be locked in exactly the same way as would happen if a second user was using the main system. Because of the real time problem, there may also be issues with provision of clinical checks - e.g. drug interactions, duplicate therapy, etc. The slave application cannot provide full decision support because it cannot view the full patient prescribing record. In any case, there may be issues with mounting data to provide prescribing decision support tools on the portable device. The decision support checking process would therefore need to take place...

Support for Training and CPD for Nonmedical Prescribers

In addition to this, the active clinical decision support that an EP system provides (drug interactions, sensitivities, cautions and contraindications) is a potentially rich source of guidance to less experienced prescribers, as long as it is implemented in such a way that warnings are clear, relevant and do not excessively impede the prescribing workflow.

Patient Care and Monitoring FN

For patients receiving oral antibiotics either prophylactically or as treatment of FN Counsel patients that initial or persistent fever should be promptly reported and that compliance with the regimen is critical. Patients should also have easy access to medical care and adequate caregiver support. Provide information on drug interactions and adverse effects.

Clinical Use and Adverse Effects of Specific Antiepileptic Drugs

IEPILEPTIC DRUG INTERACTIONS* Valproic acid is a branched-chain fatty acid that was approved for use in the United States in 1978. The enteric-coated preparation, divalproex sodium, became available in 1983. Multiple mechanisms likely contribute to its broad spectrum of action, including inhibition of sustained repetitive firing through blockade of voltage-gated Na+ channels. Valproic acid is effective against generalized and partial seizures including absence, myoclonic, and tonic-clonic seizures. High protein binding and hepatic enzyme inhibition contribute to the high incidence of drug interactions. Adverse reactions include tremor, weight gain, alopecia, hyperammonemia, carnitine deficiency, and thrombocytopenia. Fulminant hepatic failure and fatal pancreatitis have been reported. Valproate is available in 250-mg tablets and syrup (250 mg 5 ml), and divalproex sodium in 125-, 250-, and 500-mg tablets and 125-mg sprinkles for mixture with food. Rectal and parenteral formulations...

Cytochrome P450 System

Substrates are those agents that are metabolized by the cytochrome enzyme subsystems. An inhibitor may decrease or block enzyme activity required for drug metabolism and cause an elevated concentration of the circulating drug with potential to increase therapeutic or toxic effects. An inducer increases metabolic enzyme activity and results in a decreased concentration of circulating substrate drug and an increased concentration of metabolites (Pelkonen et al. 2008 Zhou 2008). This may lead to decreased therapeutic effect or to increased tox-icity due to the elevation of toxic metabolite concentrations. Knowledge of whether a drug has an inhibitory or inductive effect on a specific enzyme may help predict potential drug interactions.

History and Physical Examination

Severe illness, infections, sensory deprivation, medications, and substances of abuse causing either toxicity or withdrawal states can precipitate delirium. Use of medications confers risk both by number and by drug interaction. The risk of delirium is especially high in elders who have three or more medications initiated within a 24-hour period during hospitalization. Box 48-2 is a compilation of predisposing and precipitating risks for delirium, and Boxes 48-3 and 48-4 list medical illnesses and drugs, respectively, that can cause or contribute to delirium.

Medication Considerations in the Context of Surgery and Anesthesia

There are no current studies on outcomes to guide psychotropic medication treatment around pediatric surgical procedures. Huyse et al. (2006) proposed guidelines for the management of psychotropic medications around elective surgery. In doing so, they noted that there were limited systemic studies available to guide this area of clinical practice. They recommended consideration of the extent of the surgery, the patient's physical state, potential drug interactions, effects and side effects of psychotropic medications, risk of withdrawal symptoms, and risk of psychiatric recurrence or relapse when medication treatment is interrupted. Crone and Gabriel (2004) discussed the need to carefully assess changing pharmacokinetic parameters in patients undergoing organ transplantation. In the immediate preoperative period, medications may need to be administered at alternate times or via alternate routes when patients cannot take medications, food, or fluids by mouth. If medications are to be...

Patient Encounter 2

The increase in HMG-CoA reductase activity can be blocked with a statin, resulting in enhanced reductions in serum lipids (see section on combination therapy). Resins reduce LDL cholesterol from 15 to 30 , with a modest increase in HDL cholesterol (3 -5 ) (Table 12-8). Resins are most often used as adjuncts to statins in patients who require additional lowering of LDL cholesterol. Because these drugs are not absorbed, adverse effects are limited to the GI tract (Table 12-9). About 20 of patients taking cholestyramine or colestipol report constipation and symptoms such as flatulence and bloating. A large number of patients stop therapy because of this. Resins should be started at the lowest dose and escalated slowly over weeks to months as tolerated until the desired response is obtained. Patients should be instructed to prepare the powder formulations in 6 to 8 ounces (approximately 180-240 mL) of noncarbonated fluids, usually juice (enhances palatability) or water. Fluid...

Weaning the Overused Medications

As dosage escalates, intensity of treatment may increase as well. As the number of acute medications overused goes up, so too does the complexity of the withdrawal and the potential for drug-drug interactions as preventive medications are added. When the complexity of the patients is too great, or the doses of medications too high, it can become obvious that neither traditional outpatient approach will work for a given patient in MOH. Sometimes, the patient will have already failed in trying to do the wean at home. Sometimes the comorbid medical and psychiatric issues combine to make it very difficult to construct a reasonable outpatient plan. Sometimes drug interactions, allergies, contraindications, or intolerances are such that it appears too daunting to engage in the outpatient wean.

Levocarnitinein Libido

Adverse effects of, 423, 1426, 1427t-1428t, 1437t in chronic hepatitis B, 423 dosage of, 423, 1427t-1428t drug interactions of, 1427t-1428t in HIV infection, 1426, 1427t-1428t, 1434 mechanism of action of, 1421f resistance to, 423 Lamotrigine, 828t drug interactions of, 684 dosage of, 320, 321-322, 323, 335t, 336t drug interactions of, 321-322 in GERD, 320, 321-322, 323 in Helicobacter pylori eradication, 3351 in peptic ulcer disease, 336t Lanthanum in tuberculosis, 1262 in urinary tract infections, 1311 , 1312 Levofloxacin resistance, 1194 Levomethadyl, arrhythmia with, 179 Levonorgestrel, 843, 845 , 849, 851, 853, 875 Levorphanol dosage of, 575 in pain, 575 Levothyroxine (T4), 828 anxiety with, 694 dosage of, 769 drug interactions of, 771 in hypothyroidism, 769-771, 771 adverse effects of, 169t in arrhythmias, 1621 dosage of, 178t, 179t drug interactions of, 955t for facilitation of defibrillation, 178, 178t, 179t mechanism of action of, 162t in musculoskeletal disorders, 1025 in...

Special Populations

Treatment of elderly patients with bipolar disorder requires special care because of increased risks associated with concurrent medical conditions and drug-drug interactions. General medical conditions including endocrine, metabolic, or infectious diseases can mimic mood disorders. Patients should be evaluated for such medical ill Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions, for example, DVP and warfarin. Phar-macodynamic interactions include additive sedation and cognitive toxicity, which increase risk of falls and other impairments.

Cancer Chemotherapy and Treatment

Clinicians should play a role in chemotherapy safety, patient education, and monitoring patient response to therapy. For example, cumulative doses of anthracyc-lines should be monitored along with signs and symptoms of heart failure. Clinicians also should monitor for drug interactions between other current medications and chemotherapy agents.

Patient Encounter 2 Part 3 ITP Creating a Care Plan for ITP patient

Romiplostim and eltrombopag are effective in increasing platelet counts in patients with ITP and can be used in combination with therapies that inhibit platelet destruction. While usually well tolerated, a number of rare but serious risks have been reported, including changes in the bone marrow, worsened thrombocytopenia and the risk of bleeding after cessation of the medication, thrombotic thromboembolic complications, and worsening of blood cancers. Eltrombopag carries a black-box warning regarding hepatic toxicity. It is also associated with development of cataracts and has multiple drug-drug interactions. To enhance patient safety, both romiplostim and eltrombopag are available only through restricted access programs. For both programs, each institution must enroll in the program to receive drug and training kits and only prescribers, pharmacists, and patients registered with the program are able to prescribe, dispense, and receive the product, respectively.

Primary Care of SUD Patients

The primary care of SUD patients must take into account the systemic effects of the drug(s) ingested, route of administration, methods of drug procurement, illicit drug-prescription drug interactions, and typically, higher rates of nonad-herence to follow-up and prescribed regimens (Ries et al., 2009). Infectious diseases (e.g., HIV, hepatitis B and C, tuberculosis) and sexually transmitted infections (e.g., gonorrhea,

Transcranial Magnetic Stimulation

Currently, TMS coils follow one of 2 basic designs (Bohning, 1999). They can be either round and generate a diffuse ring of magnetic field or a Figure 8 coil in which the summation of the 2 round coils is greatest at the center. This latter design allows a more focal stimulation. Single TMS pulses can produce isolated excitatory and inhibitory events in nerve pathways such as the corticospinal system. Since TMS applied to the motor cortex can readily induce a contralateral thumb movement, the intensity needed to generate 5 movements out of 10 trials is defined as motor threshold (MT). TMS pulses can also be delivered in pairs, a few milliseconds apart (paired-pulse TMS), to probe cortical excitability by examining the influence of a first pulse onto the effect of a second pulse on motor evoked potentials (MEPs) (Ziemann et al., 2000). Finally, trains of repetitive TMS (or rTMS) are postulated to modulate the neuronal activity both distally and at the site of stimulation. TMS thus...

Acute Treatment of Episodic Migraine

Abstract All patients with migraine need to be provided acute treatment, even those on preventive medications. Setting clinical goals and expectations with patients improves adherence and outcomes. Goals for acute treatment include quick onset with consistent response, low recurrence, restoration of normal function with reduced disability, minimal side effects, and minimal use of rescue meds, at lowest possible cost. When patients are surveyed as to their desires for acute treatment and given choices, they choose a pain-free response by 2 h. Clinical pearls for acute treatment are provided, followed by specific sections on use of triptans, ergots, NSAIDs, and other nonspecific medications such as acetaminophen, butalbital, antiemetics, steroids, and narcotics. Special sections discuss the potential for drug-drug interactions, including serotonin syndrome, as well as emergency acute treatment. Keywords Acute migraine treatment Acute treatment goals Triptans Ergots NSAIDs Butalbital...

Oral Anticoagulants And Neuraxial Block

The concurrent use of medications that affect other components of the clotting mechanisms may increase the risk of bleeding complications for patients receiving oral anticoagulants, and do so without influencing the prothrombin time and INR. These medications include aspirin and other NSAIDs, and heparin. One should reflect on these drug interactions when an indwelling neuraxial catheter is being considered for a patient.

Medication Adjustment

Although oral analgesics are beyond the scope of this chapter, it should be noted that specific protocols might include the introduction and adjustment of antidepressants, anticonvulsants, ok -adrenergic agonists, nonsteroidal anti-inflammatory drugs (NSATDs), muscle relaxants, narcotics, and other medications. These protocols run concurrently with all other protocols of medical management. Consideration as to concurrent medical conditions and their associated medications, as well as the contemplated interventional therapy, is necessary to avoid adverse outcome caused by drug interaction. 93

Upon completion of the chapter the reader will be able to

Compare and contrast anticholinergics antispasmodics, a-adrenoceptor agonists, dual serotonin-norepinephrine reuptake inhibitors, vaginal estrogens, cholinomi-metics, tricyclic antidepressants (TCAs), and vasopressin analogues in terms of mechanism of action, treatment outcomes, adverse effects, and drug-drug interaction potential when used to manage UI or pediatric enuresis.

Treatment General Approach

The approach to antifungal therapy in patients with endemic fungal infections is determined by the severity of clinical presentation, the patient's underlying immunosuppression, andpotential toxicities and drug interactions associated with antifungal treatment. Immunocompetent patients with mild disease following exposure to H. capsulatum or C. immitis often experience a benign course of infection and rarely require antifungal therapy. Typically, these patients are followed in the outpatient setting with serial antigen testing to confirm resolving infection. Patients without clinical improvement within the first month are typically treated with oral itraconazole for 6 to 12 weeks (Table 84-2).14 6 Other newer azoles such as voriconazole and posaconazole appear to have good activity against endemic fungi however, there are currently insufficient data to recommend their routine first-line use. Fluconazole (400-800 mg day) is somewhat less effective than itraconazole but may have fewer...

Treating Latent Tuberculosis Infection LTBI

Niazid. ' ' Rifabutin 300 mg daily might be substituted for rifampin in patients at high risk of drug interactions. A 12-dose, once weekly regimen of isoniazid and rifapentine, a long half-life cyclopentyl-rifampin derivative, is under study. The combination of pyrazinamide and rifampin is no longer recommended because of unac-

Three Months and Beyond

Interview the patient to determine if there is worsening or new symptoms related to VTE. Inquire about and evaluate patient adherence to therapy. Ask the patient about overt bruising or bleeding as well as changes in stool or urine color. Reinforce previous patient education regarding vitamin K intake and potential drug-drug interactions with warfarin.

Therapeutic Drug Monitoring

Be particularly useful.44,46 Finally, TDM of the TB and HIV drugs is perhaps the most logical way to untangle the complex drug interactions that take place. For a complete list of drug interactions visit the CDC website at nchstp tb tb hiv drugs toc.htm.54 In particular, interactions between the rifamycins (e.g., rifampin, rifapentine, and rifabutin) and the HIV protease inhibitors and NRTIs are common and require dose and frequency modifications in many cases. Since these are constantly being updated, the preceding link is an excellent way to keep current.

Patient monitoring and side effects

Antifungals used for the treatment of endemic mycoses can be associated with clinically-significant drug interactions and toxicities, especially with the prolonged treatment courses that are often required in the management of endemic mycoses. Itraconazole is available as a capsule formulation and as a liquid. The liquid formulation of itraconazole has several advantages over the capsule it has a better oral bioavailability and does not require the low gastric pH that is required for dissolution and absorption of the capsule. However, the oral solution is somewhat dilute, has an unpalatable aftertaste (an issue when taking months of therapy), and has a much higher rate of GI side effects. Therefore, the capsule formulation is often preferred provided patients are not on acid-suppression therapy (i.e., proton pump inhibitors, histamine antagonists, or antacids). Drug interactions are an important concern in patients taking long-term azole therapy. Itraconazole is a substrate and...

Patient Encounter 4 Hormonal Contraceptives and Interactions With AEDs

LJ, a 25-year-old-woman with complex partial seizures, presents a prescription to the pharmacy for a triphasic oral contraceptive containing ethinyl estradiol and norges-timate. A review of her medication profile shows that she is taking carbamazepine extended release 1,200 mg day. Her last refill for this prescription was 2 weeks ago. She reports that she has not had a seizure for 1 year and that she just became engaged. She is planning to be married in 4 months.

Patient Encounter 1 Part 1

In children and adolescents, treatment practices are similar to the approach in adults with a focus on nonpharmacologic therapy and oral analgesics. Children younger than 2 years of age, elderly persons, and pregnant women also may need special care. Elderly patients may be more prone to systemic effects because of thinning of the skin and increased absorption of topical agents and drug interactions from poly-pharmacy.

Patient Encounter 1 New Onset Seizures

Able to monitor seizure frequency and adverse drug effects in some way. Design of an appropriate pharmacotherapeutic plan is based upon the patient's seizure type, the common adverse effect profile of possible AEDs, potential drug interactions, and economic factors (e.g., cost of the drug, insurance formulary, ability to pay). Other

Patient Care and Monitoring

Develop a treatment plan with the patient and other health care professionals if appropriate. Choose therapeutic options based on the underlying cause of nausea and vomiting, duration and severity of symptoms, comorbid conditions, medication allergies, presence of contraindications, risk of drug-drug interactions, and treatment adverse-effect profiles.

Patient Care and Monitoring Brain Metastasis

For patients receiving corticosteroids, monitor for adverse effects and drug interactions. Does the patient need GI prophylaxis for long-term treatment Slowly taper once symptoms improve and or radiation or surgery is completed. 3. Evaluate the patient for drug interactions, allergies, and adverse effects with phenytoin or corticosteroid therapy.

Outcome evaluation

Assess the effectiveness of therapy in resuming normal menstrual cycles with minimal related pain after an appropriate treatment interval (1-2 months). Assess improvement in quality-of-life measures such as physical, psychological, and social functioning and well-being. Evaluate the patient for adverse drug reactions, drug allergies, and drug interactions. Table 49-2 illustrates the common side effects that may occur for which monitoring is required. Table 49-3 illustrates the specific expected outcome measures for each of the menstruation-related disorders discussed in this chapter.

Nonpharmacologic Therapy

Behavioral and environmental modifications may significantly improve dry eye, especially in mild cases. Evaluate the patient's environment for air drafts. Consider adding a humidifier in low-humidity areas. Schedule regular breaks from computer work or reading. Lower the computer screen to below eye level to decrease lid aperture. Evaluate medication profile and therapeutically substitute medications that do not exacer-

Modifying Empirical Therapy Based on Cultures and Clinical Response

Er the antimicrobial therapy has failed Changing antimicrobials generally is one of the easiest interventions relative to other options. However, it is important to remember that antimicrobial therapy comprises only a portion of the overall disease treatment, and there may be many factors that contribute to a lack of improvement. In general, inadequate diagnosis resulting in poor initial antimicrobial or other non-antibiotic drug selection, poor source control, or the development of a new infection with a resistant organism are relatively common causes of antimicrobial failure. An infection-related diagnosis may be difficult to establish and generally has two components (a) differentiating infection from noninfection-related disease and (b) providing adequate empirical spectrum of activity if the cause is infectious. Failure of improvement in a patient's condition should warrant broadening the differential diagnosis to include noninfection-related causes, as well as considering other...

Emergency Department Treatment and Disposition

Management of patients with PCP pneumonia is complex and starts with meticulous supportive care. The initial treatment regimen is based on a number of factors, including prior PCP suppressive therapy, efficacy of treatment, patient tolerability to the treatment, severity of disease, toxicity of treatment, allergies, and drug-drug interactions. The timing of initiation of highly active antiretroviral therapy (HAART) in patients who are not already on these medications is controversial. Patients generally will improve after initiation of HAART therapy however potential risks include immune reconstruction illness and drug-drug interactions. Trimethoprim-sulfamethoxazole, orally or intravenously, is generally the first-line standard treatment. Pentamidine, clindamycin-primaquine, trimetrexate-leucovorin, atovaquone, and trimethoprim-dapsone are also effective. Treatment with corticosteroids should be initiated if the PO2 is less than 70 or the A-a gradient is greater than 35. Since...

Selection of Medication

The effectiveness of antidepressants is generally comparable across classes, and therefore selection of an antidepressant depends mainly on patient preference, side effect profile, drug interactions, previous response to a specific medication, treatment overlap with other psychiatric conditions, and cost (Tables 47-3 and 47-4). Minimal data support the increased efficacy or speed of onset for any particular agent, with response rates across clinical trials generally 50 to 75 for patients receiving active treatment. Onset of improvement typically takes 3 to 6 weeks, although the STAR*D study indicates that patients may require up to 12 to 14 weeks to achieve remission of symptoms. In fact, 40 of patients in the multiyear, multisite STAR*D study who eventually achieved remission in the first level of treatment with citalo-pram did not show a response (i.e., 50 improvement in symptoms) until week 8 of treatment (Trivedi et al., 2006). check for drug interactions in patients receiving...

Adjunctive Medication

Judicious use of additional medications may be appropriate in selected schizophrenic patients and is very frequently utilized. The basis for the use of adjunctive medication may be treatment of side effects, refractory psychotic symptoms, comorbid conditions, or specific nonpsychotic symptoms such as agitation, anxiety, depression, or mood elevation. Careful consideration of potential side effects, additive effects, and drug interactions is essential.

Relative Contraindications

Between 30 and 50 of women complain of breakthrough bleeding or spotting when oral contraceptives are initiated. These side effects tend to resolve by the third or fourth cycle.1 Before changing formulations, other more serious causes of bleeding or spotting, such as pregnancy, infection, poor absorption of the oral contraceptive owing to drug interaction, or GI problems should be ruled out. Once these causes have been ruled out, the timing of the spotting must be determined in order to adjust the formulation appropriately.

Other Chemotherapeutic Agents

Because of its monoamine oxidase inhibition, procarbazine can predispose the patients receiving it to a variety of drug interactions, including synergistic sedative effects with phenothiazines, barbiturates, and narcotics, as well as alcohol intolerance. The caution advised with other MAOIs regarding the tyramine effect with cheese or wine has not been a clinical problem with procarbazine. 1 , y , y

Principles of Prescribing

The decision to prescribe a drug depends on many factors besides age, including the patient's functional status, comor-bidities, other medications, and personal preferences and values. Physicians must be extremely vigilant in prescribing, especially for the frail elderly patient, carefully weighing the risks and benefits of any new medication. Periodic review of patients' medication list is essential to monitor for adverse effects, potentially inappropriate drugs, drug-drug interactions, and drug-disease interactions.

Pharmacokinetics and Pharmacodynamics

Knowledge of the physiologic changes that occur with aging is essential when prescribing medications to the elderly patient. Changes in pharmacokinetics and pharmacodynam-ics can result in increased or decreased amounts of medication and drug-drug interactions (Table 4-11).

Patient Centered Medical Home

The advent of the electronic medical record may be as significant as the discovery of penicillin (see Chapter 9). It will allow the family physician to incorporate the latest evidence-based recommendations into an individual's care, write electronic prescriptions, and be alerted to drug interactions while seeing a patient. Internet-based textbooks such as this one will provide immediate access to information during the patient visit.

Combination Therapy for Elevated LDL Cholesterol

A statin combined with a resin results in similar reductions in LDL cholesterol as those seen with ezetimibe. However, the magnitude of triglyceride reduction is less with a resin compared to ezetimibe, and this should be considered in patients with higher baseline triglyceride levels. In addition, gastrointestinal adverse events and potential drug interactions limit the utility of this combination.


Despite recommendations to the contrary, older people are still being excluded from clinical research on the basis of age alone, shown by an analysis of studies reported in four leading journals (BMJ, Gut, the Lancet and Thorax) which found 35 (170) excluded older people with no justifiable reason.6 Reviews of trials in acute myocardial infarction7 and Parkinson's disease,3 conditions where prevalence and incidence are strongly related to advancing age, found that trials published later were more likely to exclude older subjects. Moreover, since more women than men survive to older age and in some cases, such as cardiovascular disease, women develop diseases later in life than men, exclusion on the basis of age disproportionately disadvantages women.8 Operating an upper age limit for trials has often been used to limit the problem of co-morbid conditions and drug interactions that may occur with increasing age, in the belief that most adverse drug reactions in older people are simply...

Days 6 to

Interview the patient to determine if there is worsening or new symptoms related to VTE. Inquire about and evaluate patient adherence to therapy. Ask the patient about overt bruising or bleeding, particularly at the injection site, as well as changes in stool or urine color. Advise the patient to limit physical activity if pain persists and to elevate the extremity increase activity as tolerated. Reinforce previous patient education regarding vitamin K intake and potential drug-drug interactions with warfarin.

Adverse Effects

Drug interactions Classically, records are available in old Chinese medicinal literature on combined effects of herbs, their facilitatory and antagonistic effects. Nowadays, 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. In the area of anaesthesia, drug interactions between herbs and modern medicine could induce life-threatening reactions. Table 5.1 illustrates some studies currently done on this Table 5.1. Examples of Herb-Drug Interaction

Case Study

The system is administered by two senior pharmacists, and uses third party drug data from First DataBank Europe (FDBE) Ltd (Exeter, UK). FDBE send regular updates to the Trust, which are loaded onto the system by Trust IM&T staff, who then itemise any data changes for the attention of the system administrators. Based on FDBE data, the system provides decision support for drug interactions, sensitivities, drug-disease interactions, duplicate therapies and clinical trials management (Trust customised table). The training of new users of the system is an in-use process consisting of a combination of desk-based initial training, together with shadowing experienced users.


Toxicology is the study of the harmful effects of chemicals. Any substance that has a harmful effect on the body is known as a poison or toxin. We often think of poisons as substances that have been accidentally ingested or absorbed by an animal, e.g. slug bait. However, toxicity can also be caused by therapeutic substances, i.e. a drug used to treat one or more conditions in animals, if the dose rate is too high, the animal's response to the drug is not usual or a drug interaction has occurred.

The elderly

Any form of drug therapy in the elderly, whether with allopathic or herbal medicines, is associated with an increased risk of side effects and of those side effects having serious consequences because of decreased metabolism and pre-existing organ damage. In addition, the risk of drug interactions is greater as older people tend to suffer from several diseases and often take a number of medications.

Fungal Infections

Posaconazole (Noxafil) is a triazole antifungal that has recently been FDA approved for prophylaxis against IA in HSCT patients with GVHD and is now the recommended prophylactic agent for this subset of HSCT patients on immunosuppression.43 Posaconazole should be given with food for adequate absorption. Micafungin (Mycamine), an agent of the newer class of antifungals known as the ech-inocandins, has been FDA approved for prophylaxis of Candida infections in patients undergoing HSCT.


Medications can be administered by several routes including oral, intravenous, intramuscular, subcutaneous, rectal, transdermal, or sublingual. Drug bio-availability describes the rate and extent to which a medication's active ingredients are absorbed and made available for therapeutic action. The rate of absorption is influenced by drug formulation, drug interactions, and gastric motility. Properties that affect absorption over time include the surface area, mucosal integrity function, gastric acidity, and local blood flow. In general, gastric absorption is increased when the stomach is empty, although gastrointestinal side effects are often increased when medications are taken without food. Drugs given


Medication algorithms for childhood major depression have been developed to guide treatment, including the Texas Children's Medication Algorithm Project (Hughes et al. 2007). In the case of the physically ill child, there may be specific circumstances that influence the choice of a therapeutic agent. The choice of a specific antidepressant is usually directed by consideration of its side effects, half-life, and potential drug interactions. For example, in children with chronic pain syndromes, venlafaxine may have dual benefits in terms of its demonstrated antide-pressant and analgesic actions (Kiayias et al. 2000). For patients with low energy or attentional issues, bupropion may have additional benefits. For patients on multiple medications for their physical illness, where drug interactions are a concern, escitalo-pram may have benefits over other SSRIs commonly recognized as first-line agents, including fluoxetine.

Serotonin Syndrome

Serotonin syndrome is often described as a clinical triad of mental status changes, autonomic hyperac-tivity, and neuromuscular abnormalities, although not all of these findings are present in all patients with this disorder (Boyer and Shannon 2005 Brown et al. 2000). An excess agonism of the central and peripheral nervous system serotonergic receptors is caused by a range of drugs, including SSRIs, monoamine oxidase inhibitors (MAOIs), valproate, dex-tromethorphan, lithium, meperidine, and fentanyl. Drug-drug interactions that can cause serotonin syndrome include linezolid (an antibiotic that has MAOI properties) used with an SSRI, as well as combinations of SSRIs, trazodone, buspirone, venlafax-ine, ondansetron, metoclopramide, and sumatriptan (Boyer and Shannon 2005). Serotonin syndrome is often self-limited and may resolve spontaneously after discontinuation of the serotonergic agents. Se

Herbal Remedies

Herbal remedies, or botanicals, are supplement preparations made from various plant components. Herbals typically contain numerous chemical compounds. One study found that 34 of the U.S. population used herbal remedies at least once, and 14 took at least one herbal remedy consistently from June 2002 to June 2003 (Rogers, 2005). Chinese herbs, Ayurvedic herbs, and Latin American herbs are frequently used, but the great number of available herbs from around the world is not the only issue to discuss with patients. A given remedy's potency and efficacy are influenced by where an herb was grown, the particular species used in the formulation, how the plant products were processed, which plant parts were used, and which compounds were used for chemical standardization. Table 52-3 lists common forms of herbal preparations. Table 52-4 lists some of the most common individual herbs, with indications, efficacy, and potential adverse effects and drug interactions.

Combination Products

Drug Interactions Drug Interactions Drug Interactions Drug Interactions Drug Interactions Drug Interactions Multiple drug interactions (most based on yohimbine, not yohimbe bark extract) tricyclics, antipsychotics, clonidine, sympathomimetics Increases naloxone side effects May alter CYP metabolism Data from Basch EM, Ulbricht CE. Natural Standard Herb and Supplement Handbook The Clinical Bottom Line. Boston, Elsevier-Mosby, 2005 Blumenthal M. American Botanical Council. The ABC Clinical Guide to Herbs. New York, Thieme, 2003 Brinker F. Herb Contraindications and Drug Interactions, 3rd ed. Sandy, Oregon, Eclectic Publications, 2001 Natural Medicines Comprehensive Database (accessed November 2009) and Rotblatt M, Ziment I. Evidence-Based Herbal Medicine. Philadelphia, Hanley & Belfus, 2002. *Numbers after herbs indicate their rank in terms of the 25 best-selling herbs in the United States in 2007, as obtained from Information Resources. These data only cover about 5.6 of the total...

Common Drugs for

The following list is intended for informational purposes only. It does not include all medications you may be taking, and it does not cover all possible side effects, drug interactions, or uses of the medication. If you develop symptoms not mentioned or if you have questions, contact your doctor, nurse, or pharmacist.

Control risk factors

Angina Exercise Example Programme

Adverse treatment effects can largely be averted by avoiding drug interactions and the use of drugs that may have unfavorable effects on comorbid diseases. For example, P-blockers may exacerbate pre-existing bronchospasm. P-Blockers are not absolutely contraindicated in broncho-spastic disease, but should be avoided in patients with poorly controlled symptoms. While patients often require combination an-tianginal therapy, there is a potential pharmacodynamic drug interaction with the con-currentuse of P-blockers and nondihydropyridine CCBs. Since both drug classes slow electrical conduction through the atrioventricular (AV) node, serious bradycardia or heart block may result with their concomitant use. Appropriate drug dosing and monitoring also reduces the risk for adverse treatment effects. Drugs should be initiated in low doses, with careful up-titration as necessary to control symptoms of angina and cardiovascular risk factors.


The pharmacokinetic profiles of many anticonvulsant drugs determine dosing schedules and important drug interactions leading to potential adverse effects. Some of the older drugs, including phenytoin and sodium valproate, have a high degree of protein binding. Bioactivity may be affected by changes in the availability of binding sites. Factors which may decrease protein binding, such as competition with other drugs or a decrease in serum albumin concentration, may lead to toxicity.

Adverse Drug Effects

Table 40.13 shows a classification of drug-related complications. Although uncommon, hypersensitivity (allergy) and idiosyncratic reactions are potentially disastrous without early recognition and effective management. In contrast, drug interactions and the incorrect use of drugs are common problems. These are usually predictable, preventable and the result of human error. The risk of an adverse reaction increases in a non-linear fashion with the number of drugs given to a patient. Therefore, as polypharmacy is usual during anaesthesia, there is a substantial risk of a drug reaction.


Following a complete assessment of the patient, developing a comprehensive therapeutic plan that utilizes the fewest number of medications to achieve the highest quality of life is essential. Many times, one drug may provide relief for multiple symptoms, resulting in better patient care, lower costs, and fewer medications for the patient to take. Cost-effective drug recommendations are essential for hospice agencies to control costs, given that Medicare and most other third-party payors reimburse hospice at a fixed per-diem rate. Avoiding polypharmacy will reduce the incidence of adverse drug events related to drug interactions, excessive side effects, and duplications of therapy. The following list of symptoms addressed by palliative care includes common symptoms observed in end of life however, it is not comprehensive. Palliative care is more than just pain management. It includes the treatment of symptoms resulting in the discomfort for the patient, which may include nausea,...


Sunitinib blocks several tyrosine kinases, so it inhibits platelet-derived growth factor, vascular endothelial growth factor receptor, stem cell factor receptor, fms-like receptor growth factor, colony-stimulating growth factor receptor type 1, and glial-cell-line-derived neurotrophic factor receptor. The active metabolite of sunitinib blocks these same enzymes with similar potency. The pharmacokinetics of sunitinib demonstrate a time of peak concentration of about 5 hours, with a half-life of 41 to 86 hours.46 It is indicated for the treatment of GISTs after disease progression or intolerance to imat-inib. It is also indicated for the treatment of advanced renal cell cancer. Significant side effects include left ventricular dysfunction, hemorrhage, asthenia, hypertension, nausea and vomiting, and diarrhea. Approximately one-third of patients may develop a yellow color of the skin, along with dryness and cracking of the skin. Also, hair may become depigmented with doses of 50 mg day...


Erlotinib, whose pharmacology is not entirely understood, is believed to inhibit the intracellular phosphorylation of the EGFR. Erlotinib is about 60 absorbed after oral administration food increases bioavailability to almost 100 , however this is variable and experts recommend administering erlotinib on an empty stomach. The time to peak concentrations is approximately 4 hours after a dose. The half-life of erlotin-ib is about 36 hours, and it is eliminated predominately by CYP450 3A4. Smoking increases the clearance of erlotinib by 24 , which may result in treatment failure.4 Erlotinib is used in the treatment of nonsmall cell lung cancer and cancer of the pancreas. Side effects include interstitial lung disease, rash, diarrhea, anorexia, pruritus, conjunctivitis, and drug skin. Again, significant drug interactions have been documented with CYP450 3A4 inducers and inhibitors.


Although not FDA approved for SE, levetiracetam is a newer antiepileptic that has ideal characteristics since it does not have the significant cardiopulmonary, hepatic, and sedative side effects seen with the other agents nor does it have potentially harmful drug interactions. Both IV and oral formulations have been used in RSE patients as add-on therapy with some success, although it is unclear if levetiracetam would be


Defended.4,38-40 Approaches to the patient with delayed gastric emptying might include changing to an enteral formula containing less fat because dietary fat is associated with slower gastric emptying. Metoclopramide often is given to patients receiving gastric feedings to facilitate gastric emptying. Erythromycin is an alternative medication that may be useful in stimulating gastric motility, although it also can be associated with potentially serious drug-drug interactions. Feedings by a PEG tube may be associated with a decreased risk of aspiration compared to NG feedings.40 Patients with consistently high gastric aspirates are considered to be at higher risk of aspirating feedings into their lungs and should be considered for transition to post-pyloric feedings. Postpyloric feedings may help relieve EN-related nausea and vomiting and are preferred for patients without an intact gag reflex. An important practice to help prevent aspiration is elevation of the head of the bed to at...


Imatinib was the first FDA-approved tyrosine-kinase inhibitor. The drug was designed to block the breakpoint cluster region tyrosine kinase (BCR ABL) produced by the Philadelphia chromosome associated with chronic myelogenous leukemia and acute lymphocytic leukemia. The pharmacokinetics of imatinib demonstrate a mean time to maximum concentration of 2 to 4 hours, with a terminal half-life of 15 hours.40 Imatinib also has shown activity against GI stroma tumors (GIST) that are positive for c-kit (CD117). Numerous drug interactions have been reported for imatinib. CYP450 3A4 inducers, such as rifampicin and St. John's wort, increase the clearance of imatinib.41,42 Ketoconazole, a CYP450 3A4 inhibitor, has been shown to decrease imatinib clearance by almost 30 .43 Imatinib also may increase the exposure of simvastatin, a CYP450 3A4 substrate.44


Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P450 (CYP)3A4 or 2D6. Whether donepezil has the potential for enzyme induction is not known. Monitoring for possible increased peripheral side effects is advised when adding a

Desired Outcomes

Interactions.10 In addition to a physical exam, a thorough medical, social, and medication history with emphasis on cardiac disease must be taken before starting any treatment for ED to assess for ability to safely perform sexual activity and to assess for possible drug interactions.

Desired Outcome

It is imperative that transplant practitioners be aware of the specific advantages and disadvantages of the available immunosuppressants, as well as their adverse drug reaction and drug-drug interaction (DDI) profiles. There are generally considered to be three stages of medical immunosuppression (a) induction therapy, (b) maintenance

Days 9 to

Interview the patient to determine if there is worsening or new symptoms related to VTE. Inquire about and evaluate patient adherence to therapy. Ask the patient about overt bruising or bleeding, particularly at the injection site, as well as changes in stool or urine color. Advise the patient to elevate the extremity and increase activity as tolerated. Reinforce previous patient education regarding vitamin K intake and potential drug-drug interactions with warfarin.

Days 15 to

Interview the patient to determine if there is worsening or new symptoms related to VTE. Inquire about and evaluate patient adherence to therapy. Ask the patient about overt bruising or bleeding as well as changes in stool or urine color. Encourage the patient to increase activity as tolerated. Reinforce previous patient education regarding vitamin K intake and potential drug-drug interactions with warfarin.


Response occurs within 5 days in patients receiving 100 to 200 mg daily.16 Doses as low as 50 mg are effective, but clinical response is slow and potentially leads to resistance. Two weeks of oral itraconazole solution is as effective as fluconazole but is less well tolerated. Due to variable absorption, risk of toxicity, and potential for drug interactions, ketoconazole and itraconazole capsules are considered second-line alternatives to fluconazole.

Adapted from Ref 5

Drug interactions between antiretrovirals and between antiretrovirals and concomitant medications should be evaluated for each patient to avoid under- and or overexposure of either therapy. NNRTIs and PIs are metabolized by CYP450 enzymes and are inducers and or inhibitors of this enzyme system. In addition, some of the antiretrovirals are substrates, inhibitors, and or inducers of transporters such as P-glycoprotein, and therefore may lead to drug interactions. Information provided in Table 87-5 describes the drug interaction potential of each antiretroviral. Due to the ever-changing drug interactions with this class of medications, the regularly updated DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents are a recommended source of specific drug interactions.5