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After that order 500mg tetracycline amex, chemotherapy is used to kill cells left behind after surgery and radiation and to kill cells that may have metastasized to other sites buy 500mg tetracycline otc. Increasingly cheap tetracycline 250mg, chemotherapy is used before surgery—so-called neoadjuvant therapy—to shrink large tumors discount tetracycline online amex, and thereby permit lumpectomy in women who would otherwise require mastectomy. Antiestrogens block receptors for estrogen, whereas aromatase inhibitors block estrogen biosynthesis. In addition to chemotherapy and hormonal therapy, four other drugs —trastuzumab [Herceptin], ado-trastuzumab emtansine [Kadcyla], pertuzumab [Perjeta], and lapatinib [Tykerb]—can be used for adjuvant treatment. Lastly, patients may take denosumab [Xgeva] or zoledronate [Zometa] to minimize hypercalcemia (caused by bone metastases) and fractures (caused by bone metastases as well as hormonal therapy). Currently, two drugs are approved for preventing breast cancer in women at high risk. The other drug—tamoxifen [Nolvadex]—is approved for premenopausal and postmenopausal women. Another drug—exemestane [Aromasin] (discussed later)—can also prevent breast cancer, but currently it is only approved for breast cancer treatment. Benefits derive from depriving tumor cells of the growth- promoting influence of estrogen. Three antiestrogens—tamoxifen, toremifene, and fulvestrant—are approved for adjuvant treatment. Tamoxifen Tamoxifen [Nolvadex] is considered the gold standard for endocrine treatment of breast cancer. The drug is approved for treating established disease and for primary prevention in women at high risk. As discussed later, tamoxifen is a prodrug that must be converted to active metabolites. Receptor blockade underlies benefits in breast cancer and also underlies some adverse effects (especially hot flashes). Receptor activation leads to other beneficial effects (increased bone mineral density, reduction of low-density lipoprotein cholesterol, elevation of high-density lipoprotein cholesterol) as well as certain adverse effects (endometrial cancer and blood clots). Mechanism of Action in Breast Cancer Tamoxifen is a prodrug that undergoes hepatic conversion to active metabolites. Hence, in the absence of the influence of estradiol, the rate of tumor cell proliferation declines. Use for Treatment of Breast Cancer Tamoxifen has two treatment applications: (1) as adjuvant therapy to suppress growth of residual cancer cells after surgery and (2) as treatment of metastatic disease. Use for Prevention of Breast Cancer Tamoxifen is approved for reducing the development of breast cancer in healthy women at high risk. Unfortunately, tamoxifen increases the incidence of endometrial cancer, pulmonary embolism, and deep vein thrombosis. Hence women considering tamoxifen for chemoprevention must carefully weigh the benefits of treatment (reduced risk for breast cancer) against the risks (increased risk for endometrial cancer and thromboembolic events). To help determine who is at high risk for breast cancer, the National Cancer Institute has created an Internet-based Breast Cancer Risk Assessment Tool. When treatment is stopped, tamoxifen and its metabolites can be detected in serum for weeks. Cancer recurrence rate in poor metabolizers may be higher than in good metabolizers. Between 8% and 10% of white women have gene variants that prevent them from converting tamoxifen to its active metabolites. Adverse Effects The most common adverse effects are hot flashes, fluid retention, vaginal discharge, nausea, vomiting, and menstrual irregularities. In women with bone metastases, tamoxifen may cause transient hypercalcemia and a flare in bone pain. Because of its estrogen agonist actions, tamoxifen poses a small risk for thromboembolic events, including deep vein thrombosis, pulmonary embolism, and stroke. Tamoxifen acts as an estrogen agonist at receptors in the uterus, causing proliferation of endometrial tissue. Proliferation initially results in endometrial hyperplasia and may eventually lead to endometrial cancer. In women taking tamoxifen to treat breast cancer, the benefits clearly outweigh this risk. However, in women taking the drug to prevent breast cancer, the risk/benefit balance is less obvious. In postmenopausal women, endometrial cancer is usually caught early, owing to abnormal menstrual bleeding. As with other antiestrogens, benefits derive from depriving breast cancer cells of required hormonal stimulation. These drugs block the production of estrogen from androgenic precursors and thereby deprive breast cancer cells of the estrogen they need for growth. Aromatase inhibitors do not block production of estrogen by the ovaries and hence are of little benefit in premenopausal women. In fact, aromatase inhibitors may cause a compensatory rise in estradiol in premenopausal patients. Aromatase inhibitors are more effective than tamoxifen and have a different toxicity profile. Unlike tamoxifen, aromatase inhibitors pose no risk for endometrial cancer and only rarely cause thromboembolism. However, they can increase the risk for fractures and have been associated with moderate to severe myalgias. In postmenopausal women, the major source of estrogen is adrenal androgens, which are converted into estrogen by the enzyme aromatase in peripheral tissues. In women with estrogen-dependent cancer, estrogen deprivation can arrest tumor growth and may cause outright cell death. Anastrozole may be used as initial therapy or as a follow-up to therapy with tamoxifen. Other reactions include anorexia, vomiting, diarrhea, constipation, dyspnea, peripheral edema, vaginal hemorrhage, and hypertension. Up to 50% of women experience musculoskeletal pain, often described with the statement, “Every bone in my body hurts. For women who choose to continue anastrozole, pain can often be managed with a mild analgesic (e. To reduce bone loss, women should ensure adequate intake of calcium and vitamin D. Anastrozole is less likely to cause hot flashes, weight gain, or vaginal bleeding—although it may cause more nausea and irritability. In contrast to tamoxifen, anastrozole is devoid of all estrogenic activity and hence does not promote endometrial cancer or thromboembolic events—although it does increase the risk for fractures. Other reactions include headache, arthralgia, fatigue, constipation, dyspnea, cough, vomiting, diarrhea, and hot flashes. Like anastrozole, and unlike tamoxifen, letrozole poses no risk for endometrial cancer. Like anastrozole, exemestane inhibits aromatase and thereby reduces estrogen levels. A dosage of 25 mg once daily (administered after a meal) can reduce circulating estrogen by 85% to 95%. In addition to treating breast cancer, exemestane can be effective for breast cancer prevention; however, it does not yet have approval for this indication. Exemestane is rapidly absorbed after oral dosing and is widely distributed to tissues. The most common adverse effects are fatigue, nausea, hot flashes, depression, and weight gain. Women at high risk for osteoporosis can be treated with denosumab [Prolia] or a bisphosphonate (e. For treatment of breast cancer, trastuzumab may be used (1) alone in women who failed to respond to prior chemotherapy, (2) in combination with paclitaxel as first-line therapy, and (3) for adjuvant treatment as part of a regimen containing doxorubicin, cyclophosphamide, and paclitaxel. Adverse Effects The principal concern with trastuzumab is cardiotoxicity, manifesting as ventricular dysfunction and congestive heart failure. Because of cardiotoxicity, trastuzumab should be used with caution in women with preexisting heart disease.
The simple occupancy theory states that the intensity of response to a drug is proportional to the number of receptors occupied; maximal response is reached with 100% receptor occupancy tetracycline 500mg sale. Because the hypothetical cell in this figure has only four receptors purchase tetracycline 250mg visa, maximal response is achieved when all four receptors are occupied buy tetracycline with a mastercard. Specifically buy tetracycline cheap online, there is nothing in this theory to explain why one drug should be more potent than another. In addition, this theory cannot explain how one drug can have higher maximal efficacy than another. That is, according to this theory, two drugs acting at the same receptor should produce the same maximal effect, provided that their dosages were high enough to produce 100% receptor occupancy. However, at 100% receptor occupancy, the response elicited by pentazocine is less than that elicited by meperidine. Modified Occupancy Theory The modified occupancy theory of drug-receptor interaction explains certain observations that cannot be accounted for with the simple occupancy theory. The modified theory ascribes two qualities to drugs: affinity and intrinsic activity. The term affinity refers to the strength of the attraction between a drug and its receptor. Intrinsic activity refers to the ability of a drug to activate the receptor after binding. Affinity As noted, the term affinity refers to the strength of the attraction between a drug and its receptor. Because they are strongly attracted to their receptors, drugs with high affinity can bind to their receptors when present in low concentrations. Because they bind to receptors at low concentrations, drugs with high affinity are effective in low doses. Conversely, drugs with low affinity must be present in high concentrations to bind to their receptors. Intrinsic Activity The term intrinsic activity refers to the ability of a drug to activate a receptor upon binding. That is, by causing intense receptor activation, they are able to cause intense responses. It should be noted that, under the modified occupancy theory, the intensity of the response to a drug is still related to the number of receptors occupied. The wrinkle added by the modified theory is that intensity is also related to the ability of the drug to activate receptors after binding has occurred. Under the modified theory, two drugs can occupy the same number of receptors but produce effects of different intensity; the drug with greater intrinsic activity will produce the more intense response. Agonists, Antagonists, and Partial Agonists As previously noted, when drugs bind to receptors they can do one of two things: they can either mimic the action of endogenous regulatory molecules or they can block the action of endogenous regulatory molecules. Like agonists, partial agonists also mimic the actions of endogenous regulatory molecules, but they produce responses of intermediate intensity. Because neurotransmitters, hormones, and other endogenous regulators activate the receptors to which they bind, all of these compounds are considered agonists. In terms of the modified occupancy theory, an agonist is a drug that has both affinity and high intrinsic activity. Affinity allows the agonist to bind to receptors, whereas intrinsic activity allows the bound agonist to activate or turn on receptor function. Antagonists Antagonists produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs. In terms of the modified occupancy theory, an antagonist is a drug with affinity for a receptor but with no intrinsic activity. Affinity allows the antagonist to bind to receptors, but lack of intrinsic activity prevents the bound antagonist from causing receptor activation. Although antagonists do not cause receptor activation, they most certainly do produce pharmacologic effects. Antagonists produce their effects by preventing the activation of receptors by endogenous regulatory molecules. Antihistamines, for example, are histamine receptor antagonists that suppress allergy symptoms by binding to receptors for histamine, thereby preventing activation of these receptors by histamine released in response to allergens. It is important to note that the response to an antagonist is determined by how much agonist is present. Because antagonists act by preventing receptor activation, if there is no agonist present, administration of an antagonist will have no observable effect; the drug will bind to its receptors, but nothing will happen. On the other hand, if receptors are undergoing activation by agonists, administration of an antagonist will shut the process down, resulting in an observable response. An example is the use of the opioid antagonist naloxone, which is used to block opioid receptors in the event of an opioid overdose. Antagonists can be subdivided into two major classes: (1) noncompetitive antagonists and (2) competitive antagonists. Noncompetitive (Insurmountable) Antagonists Noncompetitive antagonists bind irreversibly to receptors. The effect of irreversible binding is equivalent to reducing the total number of receptors available for activation by an agonist. Because the intensity of the response to an agonist is proportional to the total number of receptors occupied, and because noncompetitive antagonists decrease the number of receptors available for activation, noncompetitive antagonists reduce the maximal response that an agonist can elicit. Dose-response curves illustrating inhibition by a noncompetitive antagonist are shown in Fig. A, Effect of a noncompetitive antagonist on the dose- response curve of an agonist. Note that noncompetitive antagonists decrease the maximal response achievable with an agonist. Competitive antagonists simply increase the amount of agonist required to produce any given intensity of response. Because the binding of noncompetitive antagonists is irreversible, inhibition by these agents cannot be overcome, no matter how much agonist may be available. Although noncompetitive antagonists bind irreversibly, this does not mean that their effects last forever. Consequently, the effects of noncompetitive antagonists wear off as the receptors to which they are bound are replaced. Because the life cycle of a receptor can be relatively short, the effects of noncompetitive antagonists m ay subside in a few days. Still, this can be a long time for some functions; therefore, these agents are rarely used therapeutically. Competitive (Surmountable) Antagonists Competitive antagonists bind reversibly to receptors. As their name implies, competitive antagonists produce receptor blockade by competing with agonists for receptor binding. If an agonist and a competitive antagonist have equal affinity for a particular receptor, then the receptor will be occupied by whichever agent—agonist or antagonist—is present in the highest concentration. If there are more antagonist molecules present than agonist molecules, antagonist molecules will occupy the receptors and receptor activation will be blocked. Conversely, if agonist molecules outnumber the antagonists, receptors will be occupied mainly by the agonist and little inhibition will occur. Because competitive antagonists bind reversibly to receptors, the inhibition they cause is surmountable. In the presence of sufficiently high amounts of agonist, agonist molecules will occupy all receptors and inhibition will be completely overcome. Partial Agonists A partial agonist is an agonist that has only moderate intrinsic activity. As a result, the maximal effect that a partial agonist can produce is lower than that of a full agonist. Partial agonists are interesting in that they can act as antagonists as well as agonists. For example, when pentazocine is administered by itself, it occupies opioid receptors and produces moderate relief of pain. However, if a patient is already taking meperidine (a full agonist at opioid receptors) and is then given a large dose of pentazocine, pentazocine will occupy the opioid receptors and prevent their activation by meperidine.
Accordingly purchase tetracycline overnight, the test should be performed only if epinephrine and facilities for respiratory support are immediately available order 500mg tetracycline fast delivery. Current guidelines recommend skin testing with two reagents discount tetracycline 500mg amex, which test for the major and minor determinants of penicillin allergy best tetracycline 500mg. The minor determinants, although less common, mediate most severe penicillin reactions. The major determinant reagent, available commercially as Pre-Pen, contains a single component: benzylpenicilloyl-polylysine. Benzylpenicilloyl-polylysine is a large polymeric molecule that is poorly absorbed. Hence, even in patients with severe penicillin allergy, this skin test carries a low risk for a systemic reaction. The recommended minor determinant reagent, which is not available commercially, is a mixture of three compounds: benzylpenicillin G, benzylpenicilloate, and penicilloyl propylamine. As noted, the term minor indicates that the antibodies being tested for are relatively uncommon and not that the allergic response mediated by these antibodies is of minor significance. In fact, the minor determinants are responsible for most severe penicillin reactions. Management of Patients With a History of Penicillin Allergy All patients who are candidates for penicillin therapy should be asked if they have penicillin allergy and what the reaction is. However, if there is a history of anaphylaxis or some other severe allergic reaction, it is prudent to avoid cephalosporins as well (because there is about a 1% risk for cross sensitivity to cephalosporins). When a cephalosporin is indicated, an oral cephalosporin is preferred (because the risk for a severe reaction is lower than with parenteral therapy). For many infections, vancomycin, erythromycin, and clindamycin are effective and safe alternatives for patients with penicillin allergy. Rarely, a patient with a history of anaphylaxis may have a life-threatening infection (e. In these cases, the potential benefits of penicillin therapy outweigh the risks, and treatment should be instituted. To minimize the chances of an anaphylactic reaction, penicillin should be administered according to a desensitization schedule. In this procedure, an initial small dose is followed at 60-minute intervals by progressively larger doses until the full therapeutic dose has been achieved. Accordingly, epinephrine and facilities for respiratory support should be immediately available. Children/adolescents Penicillins are a common drug used to treat bacterial infections in children. Data are lacking regarding transmission of women some other penicillins from mother to infant through breast milk. Drug Interactions Bacteriostatic Antibiotics Because penicillins are most effective against actively growing bacteria, concurrent use of a bacteriostatic antibiotic (e. Nonetheless, combined use of penicillin and bacteriostatic agents is generally avoided. The principal difference is acid stability: Penicillin V is stable in stomach acid, whereas penicillin G is not. Because of its acid stability, penicillin V has replaced penicillin G for oral therapy. Penicillinase-Resistant Penicillins (Antistaphylococcal Penicillins) By altering the penicillin side chain, pharmaceutical chemists have created a group of penicillins that are highly resistant to inactivation by beta-lactamases. In the United States three such drugs are available: nafcillin, oxacillin, and dicloxacillin. These agents have a very narrow antimicrobial spectrum and are used only against penicillinase-producing strains of staphylococci (S. Because most strains of staphylococci produce penicillinase, the penicillinase-resistant penicillins are drugs of choice for most staphylococcal infections. It should be noted that these agents should not be used against infections caused by non–penicillinase-producing staphylococci because they are less active than penicillin G against these bacteria. Oxacillin and Dicloxacillin Oxacillin and dicloxacillin are similar in structure and pharmacokinetic properties. Broad-Spectrum Penicillins (Aminopenicillins) Only two broad-spectrum penicillins are available: ampicillin and amoxicillin. Both have the same antimicrobial spectrum as penicillin G, plus increased activity against certain gram-negative bacilli, including Haemophilus influenzae, Escherichia coli, and Salmonella and Shigella species. This broadened spectrum is due in large part to an increased ability to penetrate the gram-negative cell envelope. Both drugs are readily inactivated by beta-lactamases and hence are ineffective against most infections caused by S. The drug is useful against infections caused by Enterococcus fecalis, Proteus mirabilis, E. The most common side effects are rash and diarrhea, both of which occur more frequently with ampicillin than with any other penicillin. As discussed later, ampicillin is also available in a fixed-dose combination with sulbactam, an inhibitor of bacterial beta-lactamase. Amoxicillin Amoxicillin [Moxatag] is similar to ampicillin in structure and actions. The drugs differ primarily in acid stability, amoxicillin being the more acid stable. Hence, when the two are administered orally in equivalent doses, blood levels of amoxicillin are greater. Amoxicillin produces less diarrhea than ampicillin, perhaps because less amoxicillin remains unabsorbed in the intestine. As discussed later, amoxicillin is also available in a fixed-dose combination with clavulanic acid, an inhibitor of bacterial beta-lactamases. Extended-Spectrum Penicillins (Antipseudomonal Penicillins) Only one extended-spectrum penicillin is available: piperacillin. The antimicrobial spectrum of piperacillin includes organisms that are susceptible to the aminopenicillins plus Pseudomonas aeruginosa, Enterobacter species, Proteus species (indole positive), Bacteroides fragilis, and many Klebsiella species. This extended-spectrum penicillin is susceptible to beta-lactamases and hence is ineffective against most strains of S. These infections often occur in the immunocompromised host and can be very difficult to eradicate. To increase killing of Pseudomonas, an antipseudomonal aminoglycoside (gentamicin, tobramycin, amikacin, netilmicin) may be added to the regimen. Piperacillin Piperacillin has a broad antimicrobial spectrum; however, the drug is penicillinase sensitive. As discussed later, piperacillin is also available in a fixed-dose combination with tazobactam, a beta-lactamase inhibitor. Penicillins Combined With a Beta-Lactamase Inhibitor As their name indicates, beta-lactamase inhibitors are drugs that inhibit bacterial beta-lactamases. By combining a beta-lactamase inhibitor with a penicillinase- sensitive penicillin, we can extend the antimicrobial spectrum of the penicillin. In the United States three beta-lactamase inhibitors are used: sulbactam, tazobactam, and clavulanic acid (clavulanate). Four such combination products are available: • Ampicillin/sulbactam [Unasyn] • Amoxicillin/clavulanate [Augmentin, Clavulin ] • Piperacillin/tazobactam [Zosyn, Tazocin ] Because beta-lactamase inhibitors have minimal toxicity, any adverse effects that occur with the combination products are due to the penicillin. Much of the chapter focuses on the cephalosporins, our most widely used antibacterial drugs. With only three exceptions—vancomycin, telavancin, and fosfomycin— the agents addressed here are beta-lactam drugs. Cephalosporins The cephalosporins are beta-lactam antibiotics similar in structure and actions to the penicillins. These drugs are bactericidal, often resistant to beta-lactamases, and active against a broad spectrum of pathogens. Because of these attributes, the cephalosporins are popular therapeutic agents and constitute our most widely used group of antibiotics. Mechanism of Action The cephalosporins are bactericidal drugs with a mechanism like that of the penicillins. Like the penicillins, cephalosporins are most effective against cells undergoing active growth and division. Resistance The principal cause of cephalosporin resistance is production of beta-lactamases, enzymes that cleave the beta-lactam ring and thereby render these drugs inactive.
Ovarian cyst rupture and haemorrhage usually occur in association with physiological functional cysts and are generally self-limiting generic tetracycline 250 mg amex. The majority of ovarian cyst torsion occurs in the reproductive age but about one-quarter of cases occur in children buy discount tetracycline 500mg on line. Cysts of this size are usually lifted over the confines of the pelvis and become more freely mobile purchase discount tetracycline line. The tube and ovary usually undergo torsion as a single unit order tetracycline 250 mg fast delivery, rotating around the broad ligament as an axis. In the absence of an ovarian cyst, the torsion occurs where there is an unusually long pedicle. This causes occlusion of the venous return followed later by occlusion of the arterial inflow to the ovarian tumour. An ultrasound scan shows an oedematous ovary with peripheral displacement of the follicles. Ovarian torsions occur twice as ofen with the right adnexa than with the lef adnexa suggesting anatomic diferences such as the presence of the sigmoid colon (it restricts the mobility of the lef ovary). In accordance with Kushner’s rule, the right ovary twists in a clockwise manner and the lef counterclockwise. Management Most cases of ovarian torsion require surgical intervention except in mild and early cases where there is the possibility of untwisting naturally. This woman should be managed surgically and the approach can be laparotomy or laparoscopy. If the ovarian tissue can be preserved (if the ovary appears viable), an ovarian cystectomy should be performed, while unilateral oophorectomy is considered in the worst case scenario where the ovary is non-viable. The risk is reduced with antenatal corticosteroids, but there are concerns about potential long-term adverse efects. Evidence suggests that the regret rate is higher and that the failure rate from sterilisation associated with pregnancy may be higher than that from an interval procedure. If sterilisation is to be performed at the same time as a caesarean delivery, counselling and agreement should have been given at least 2 weeks prior to the procedure. If the patient is symptomatic at follow-up, an endo-anal ultrasound or a rectal manometry should be arranged prior to a secondary repair by a surgeon with appropriate expertise. Patients who reported being satisfed with the NovaSure procedure ranged from 85% to 94%. In randomised controlled trials with other global endometrial ablation modalities, amenorrhea rates at 12 months with the NovaSure procedure ranged from 43% to 56%, while other modalities ranged from 8% to 24%. By 60 months post-procedure, 75% of the patients reported amenorrhea and 2% reported menorrhagia. Ten-year literature review of global endometrial ablation with the NovaSure® device. A 48-year-old woman undergoes laparoscopic hysterectomy and bilateral salpingo-oophorectomy, pelvic lymphadenectomy and peritoneal washings for grade 3 endometrial cancer. Which of the following is not a sign or symptom of urinary tract injury in her case? Poor urine output in the presence of normal postoperative observations – urine leaking into peritoneal cavity c. Persistent very heavily bloodstained urine postoperatively with later leakage of fuid into the vagina f. A 48-year-old woman undergoes hysterectomy and bilateral salpingo- oophorectomy, pelvic lymphadenectomy and peritoneal washings for grade 3 199 endometrial cancer. You are the registrar on call for gynaecology and have been asked to review this woman whose urine output is 20 mL for the previous 8 hours (day 1 of the operation). The operation notes reveal that this was a difcult operation due to extensive bowel and pelvic adhesions. What is most important investigation that would help in making a diagnosis of ureteric injury or occlusion? A 48-year-old woman undergoes laparoscopic hysterectomy and bilateral salpingo-oophorectomy, pelvic lymphadenectomy, bowel and pelvic adhesiolysis and peritoneal washings for grade 3 endometrial cancer. While dissecting the pelvic side wall, the consultant notices right ureteric injury close to the bladder edge. Ureteric re-implantation into the bladder using a psoas hitch to relieve tension of the repair 5. A 44-year-old woman undergoes laparoscopic subtotal hysterectomy for fbroids with a blood loss of 500 mL. You are the registrar on call and have been asked to review this woman and make a plan of management. The drain fuid creatinine level is representative of serum creatinine level and is not signifcantly higher; therefore, there is no concern of urinoma in this case. With severe endometriosis, 65% of patients could have the ureteric involvement and a further 5. The common sites of ureteric damage include the following: • At the angle of the vagina • Near the pelvic brim close to the ovarian blood supply The damage may be direct during the operation or due to avascular necrosis due to compromised vasculature. The former present early (frst few days) and the latter may present 7–10 days afer the procedure. If identifed early, stenting of the ureter alone can be sufcient to resolve the damage. Urological opinion should be sought for any suspected or obvious ureteric injuries. Urinary tract injuries in laparoscopic gynaecological surgery; Prevention, recognition and management. Women can present with abdominal pain or low-grade temperature or with vaginal discharge. Ofen (small collection of the vault), the haematoma can be drained through a vaginal approach (through vault). Often we are so concerned with obtaining the right diagnosis and making our patient well that we overlook key pieces of information, including patient financial status. When patients cannot afford the drug you prescribe, they may not get well, even though they want to be compliant. It is of critical importance that providers ask patients if they have difficulty obtaining their medication because it is cost prohibitive. If you find that your patient is having difficulty purchasing the prescribed medications, consider changing pharmacies or drug regimens. In addition, many corporations have created generic $4 lists or special prescription programs that allow patients to fill their medications for a reasonable cost. As a prescriber, you need to be familiar with the local resources for medication assistance and low-cost medications. Guidelines When in doubt, follow current guidelines for the treatment of a particular disease or symptom. Almost all medical and nursing societies have published guidelines, including the American Heart Association, the American College of Cardiology, the Infectious Diseases Society of America, and the American Diabetes Association. Although closely following the guidelines is desirable, we must always take into account that our patients may not fit well into these guidelines and that individualized care is always best. In these cases, it is important to document the rationale for deviating from standard of care. Availability Every facility and pharmacy provides drugs according to a selected formulary. The formulary may also depend on regional and national drug supplies, drug costs and available rebates, and the presence of generic medications on the market. In short, the drug you want may not be available in your facility or at a specific pharmacy. Become familiar with the formulary where you are employed, and know that it can change over time. Often there are substitutes or similar medications you can order in place of what you originally intended. For example, omeprazole may be indicated for the treatment of erosive esophagitis, but the formulary contains esomeprazole instead.