By F. Sigmor. Carlow College.
Sucrose (table sugar) and other oral carbohydrates do not relieve • Omitting or delaying meals hypoglycemia because the presence of acarbose or miglitol pre- • An excessive or incorrect dose of insulin or an oral agent that vents their digestion and absorption from the gastrointestinal tract order 200 mg aciclovir visa. Therefore order 400mg aciclovir with mastercard, the treatment choices renal insufﬁciency) are parenteral glucose or glucagon purchase 200mg aciclovir free shipping. It acts rapidly to raise blood glucose levels and arouse the than SC client buy aciclovir 400 mg lowest price. If the client is at home or elsewhere, glucagon may be given • Drug interactions that decrease blood glucose levels if available and there is someone to inject it. A family member or • Increased physical exertion roommate may be taught to give glucagon SC or IM. Glucagon is a pan- Hormones That Raise Blood Sugar creatic hormone that increases blood sugar by converting liver Normally, when hypoglycemia occurs, several hormones (glucagon, glycogen to glucose. It is effective only when liver glycogen is pres- epinephrine, growth hormone, and cortisol) work to restore and ent. Some clients cannot respond to glucagon because glycogen maintain blood glucose levels. Glucagon and epinephrine, the stores are depleted by such conditions as starvation, adrenal insufﬁ- dominant counter-regulatory hormones, act rapidly because they ciency, or chronic hypoglycemia. The hyperglycemic effect of are activated as soon as blood glucose levels start declining. People with diabetes who develop hypoglycemia may have Caution is needed in the treatment of hypoglycemia. Although impaired secretion of these hormones, especially those with type the main goal of treatment is to relieve hypoglycemia and restore the 1 diabetes. The client having a hypoglycemic re- cretion of epinephrine also occurs in people who have been action should not use it as an excuse to eat high-caloric foods or treated with insulin for several years. Health care personnel caring for the client creases tachycardia, a common sign of hypoglycemia, and may should avoid giving excessive amounts of glucose. Posthypoglycemia Care The Conscious Client Once hypoglycemia is relieved, the person should have a snack or Treatment of hypoglycemic reactions consists of immediate ad- a meal. Slowly absorbed carbohydrate and protein foods, such as ministration of a rapidly absorbed carbohydrate. For the conscious milk, cheese, and bread, are needed to replace glycogen stores in client who is able to swallow, the carbohydrate is given orally. In addition, the episode needs to include: be evaluated for precipitating factors so that these can be mini- • Two sugar cubes or 1 to 2 teaspoons of sugar, syrup, honey, mized to prevent future episodes. Repeated episodes mean that the or jelly therapeutic regimen and client compliance must be re-evaluated • Two or three small pieces of candy or eight Lifesaver candies and adjusted if indicated. Glitazones tion increases or restores the effectiveness of circulating insulin and results in increased uptake of glucose by pe- • These drugs, pioglitazone and rosiglitazone, are also ripheral tissues and decreased production of glucose by called thiazolidinediones or TZDs and insulin sensitizers. The drugs stimulate exercise or in combination with insulin, metformin, or receptors on muscle, fat, and liver cells. The drugs lower blood sugar by decreasing absorption or production of glucose, by increasing secretion of insulin, or by increasing the effectiveness of available insulin (decreasing insulin resistance). They are also con- should be skipped; if a meal is added, a drug dose traindicated in clients who are hypersensitive to them. Glitazones increase plasma volume and may cause HERBAL AND DIETARY fluid retention and heart failure. In people who did not With most herbs and dietary supplements, even the commonly take a glitazone, 2. Thus, anyone with diabetes who Meglitinides wishes to take an herbal or dietary supplement should consult • Nateglinide and repaglinide are nonsulfonylureas that a health care provider, read product labels carefully, seek the lower blood sugar by stimulating pancreatic secretion of most authoritative information available, and monitor blood insulin. Described • They can be used as monotherapy with diet and exercise below are some products that reportedly affect blood sugar and or in combination with metformin. They are metabolized in the liver; Blood Glucose Levels metabolites are excreted in urine and feces. After a dose of 2 mg is reached, increase dose in increments of 2 mg or less at 1- to 2-week inter- vals, based on blood glucose levels. In combination with insulin, PO 8 mg once daily with the ﬁrst main meal.
Those available for therapeutic use include colony- mune system malfunction buy cheap aciclovir 800 mg line, so the antiviral drugs indirectly stimulating factors (CSF; eg cheap aciclovir 400mg with amex, darbepoetin alfa cheap 400 mg aciclovir with amex, epoetin alfa order 800 mg aciclovir mastercard, improve immunologic function. These drugs, which are the primary focus of this GENERAL CHARACTERISTICS chapter, are described in the following sections and in Drugs at a Glance: Hematopoietic and Immunostimulant Agents. OF HEMATOPOIETIC AND Bacillus Calmette-Guérin (BCG) vaccine, used in the treat- IMMUNOSTIMULANT DRUGS ment of bladder cancer, is also discussed. Other drugs with immunostimulant properties are discussed in other chapters. Most hematopoietic and immunostimulant drugs are These include traditional immunizing agents (see Chap. Techniques of molecu- phages and T cells and is used with ﬂuorouracil in the treat- (text continues on page 660) 657 658 SECTION 7 DRUGS AFFECTING HEMATOPOIESIS AND THE IMMUNE SYSTEM Drugs at a Glance: Hematopoietic and Immunostimulant Agents Generic/Trade Name Indications for Use Routes and Dosage Ranges Comments Hematopoietic Agents Darbepoetin alfa (Aranesp) Anemia associated with chronic SC, IV, 0. Collection of peripheral stem cells, SC, 10 mcg/kg/d for 6–7 d, with collection on the last 3 d of drug administration Severe, chronic neutropenia, SC 5 or 6 mcg/kg, once or twice daily, depending on clinical re- sponse and ANC Pegﬁlgrastim (Neulasta) To prevent infection in patients SC 6 mg once per chemotherapy with neutropenia induced by cycle. Do not give between cancer chemotherapy 14 d before and 24 h after cytotoxic chemotherapy. Sargramostim (GM-CSF) After bone marrow transplanta- Bone marrow reconstitution, (Leukine) tion to promote bone marrow IV infusion over 2 h, 250 function or to treat graft fail- mcg/m2/d, starting 2–4 h ure or delayed function after bone marrow infusion, Mobilization of stem cells in and continuing for 21 d peripheral blood so they can Graft failure or delay, IV infusion be collected. Course of treatment may be re- peated after 7 d off therapy if engraftment has not occurred. Mobilization of stem cells, SC or IV over 24 h, 250 mcg/m2/d CHAPTER 44 HEMATOPOIETIC AND IMMUNOSTIMULANT DRUGS 659 Drugs at a Glance: Hematopoietic and Immunostimulant Agents (continued) Generic/Trade Name Indications for Use Routes and Dosage Ranges Comments Interleukins Aldesleukin (interleukin-2) Metastatic renal cell carcinoma IV infusion over 15 min Adverse reactions are common (Proleukin) in adults* 600,000 IU or 0. Oprelvekin (Neumega) Prevention of severe thrombocy- SC, 50 mcg/kg once daily Start 6–24 h after completion of topenia with antineoplastic chemotherapy and continue chemotherapy that depresses until postnadir platelet count bone marrow function in is 50,000 cells/mm3 or clients with nonmyeloid malig- higher, usually 10–21 d. Give all doses three times weekly, with at least 48 h between doses Interferon beta-1b (Betaseron) Same as Interferon beta-1a SC, 0. Repeat once weekly for 6 wk, then give one dose monthly for 6–12 mo (TICE BCG) or one dose at 3, 6, 12, 18, and 24 mo (TheraCys). AIDS, acquired immunodeﬁciency syndrome; ANC, absolute neutrophil count. These genes are then inserted Some newer formulations (eg, darbepoetin alfa, pegﬁl- into bacteria (usually Escherichia coli) or yeasts capable grastim, and peginterferon alfa 2b) can be given less of producing the substances exogenously. An additional consideration is that the sub- genes that encode interferons, for example, has made it stances are powerful biologic response modiﬁers and possible to produce large amounts of these substances they can cause unanticipated adverse effects. Exogenous drug preparations have the same mecha- terferon beta-1b) are synthetic versions of deoxyribonu- nisms of action as the endogenous products described cleic acid (DNA) recombinant products. Despite extensive research efforts, relatively few surfaces of immature blood cells in the bone marrow cytokine-like drugs are available for clinical use. One and increase the number, maturity, and functional abil- of the difﬁculties in using cytokines is maintaining ef- ity of the cells. Interferons, called alfa, beta, or gamma fective dose levels over treatment periods of weeks or according to speciﬁc characteristics, also bind to spe- months. During a natural immune response, inter- ciﬁc cell surface receptors and alter intracellular activ- acting body cells produce adequate concentrations of ities. In viral infections, they induce enzymes that cytokines around target cells. However, achieving ad- inhibit protein synthesis and degrade viral ribonucleic equate local concentrations from injected, exogenous acid. CHAPTER 44 HEMATOPOIETIC AND IMMUNOSTIMULANT DRUGS 661 In addition to their antiviral effects, interferons also with chronic renal failure, and peak plasma levels occur in have antiproliferative and immunoregulatory activities. They can increase expression of major histocompatibil- ity complex (MHC) molecules, augment the activity of Colony Stimulating Factors natural killer (NK) cells, increase the effectiveness of antigen presenting cells in inducing the proliferation Filgrastim and sargramostim are drug formulations of gran- of cytotoxic T cells, aid the attachment of cytotoxic ulocyte colony stimulating factor (G-CSF) and granulocyte T cells to target cells, and inhibit angiogenesis. Because macrophage colony stimulating factor (GM-CSF), respec- of these characteristics, the interferons are used mainly tively, produced by recombinant DNA technology. In chronic he- used to stimulate blood cell production by the bone marrow in patitis C, interferon improves liver function in approxi- clients with bone marrow transplantation or chemotherapy- mately 50% of clients, but relapse often occurs when induced neutropenia.
Epidemi- treatment of chronic schizophrenia: twelve months ological buy 200 mg aciclovir with amex, systemic and social context: an integra- follow-up buy generic aciclovir 400mg line. The omnipotence of behavioural methods of treating drug-resistant voices: testing the validity of cognitive model purchase aciclovir 400mg fast delivery. The effects of neurocognitive remedi- Psychiat Epidemiol (1993) 28: 5–10 discount 800mg aciclovir with mastercard. Cognitive-behaviour therapy for Consult Clin Psychol (1996) 64: 295–304. The design of the trial and statistical Most of the illustrative examples, however, will analysis of the results have to be appropriate refer to the treatment of depression. Psychotherapy involves complex the start, despite pointing out all of its poten- interactions between patient and therapist and tial problems, I will assume that by far the best sometimes (as in group therapy) involves the way of trying to estimate treatment effects is via interaction of a group of patients with each other the use of a randomised controlled trial (RCT). It is not as sim- I have little sympathy with the increasingly pop- ple as taking a tablet! A psychotherapy trial is ular view that we can learn much of real value likely to be far more complex, both in its imple- about treatment effects from systematically col- mentation and in the analysis and interpretation lected outcome data in routine clinical practice of the subsequent results, than most drug trials. Nor do I There are also far more opportunities for invalid have any sympathy for the often-heard view that inferences concerning treatment effects. RCTs and the use of statistical methods are inap- First, and often primarily, we are concerned propriate vehicles for the evaluation of something with internal validity: the valid estimation of a as complex as psychotherapy. Are the group differences we see the causal Textbook of Clinical Trials. Green 2004 John Wiley & Sons, Ltd ISBN: 0-471-98787-5 298 TEXTBOOK OF CLINICAL TRIALS effects of treatment? Or can they be explained by In the above paragraph we are trying to ﬁnd a other factors? Later we may be concerned with way to estimate what may be called the causal external validity: generalisation of the inferred effect of a treatment. The essence of the solution causal effects to other patients, therapists, treat- to the problem is a comparison. For each of ment centres and, perhaps, other forms of psy- the three patients, Mr Smith, Mrs Jones and chotherapy. The ﬁrst of causality and its use in the estimation of treat- is to receive therapy and have the severity of ment effects. The second and non-adherence to treatment, can be found is to fail to get the offered help, but again in Dunn. It has two possible values, THE CAUSAL EFFECT OF TREATMENT T = t (therapy) and T = c (no therapy). Let i indicate Mr Smith has suffered from severe depression, the identity of the patient (i = 1 for Mr Smith, 2 on and off, for several years. Finally, let family doctor advised him to undergo a course YT (i) indicate the ﬁnal BDI score for patient i of psychotherapy. Therearetwo had several what he thinks were very helpful potential outcomes for each of the three patients, sessions with the psychotherapist, and now is as indicated in the following table: feeling considerably better. Putting it another way, Mr Smith Y (t 1 c(1) what proportion, if any, of the drop from 20 Mrs Jones Y (t 2 c(2) to 10 points might be attributed to the receipt Mr Adams Y (t 3 c(3) of therapy? Unfortunately, it can never managed to keep any of her appointments and be observed. The obvious problem is that each has not received any help from the therapist. A patient receives one of the treatment conditions, third patient, Mr Adams, refused outright to have or the other, but not both. That present BDI score is 12 and that for Mr Adams is, the ith patient provides a value for either is 15. Mr Smith provides ask what would have been the effect of therapy Y (t 1) but not Yc(1), Mrs Jones provides Yc(2) offered if they had actually received it? Expressed the effects of different types of psychotherapy, mathematically: or to the comparison of a speciﬁc type of psy- chotherapy with, for example, a psychopharma- E[Y (i)t ] = E[Y (i)t |T = t] = E[Y (i)t |T = c] cological intervention such as a tricyclic antide- (3) pressant. If we are able to do this t c large population of eligible patients – the target then we have replaced an impossible-to-observe population about which we wish to draw causal causal effect on an individual patient with a inferences about the value of psychotherapy possible-to-estimate average of the causal effects or counselling.
Discuss nitrate antianginals in terms of indica- for use buy aciclovir 400mg overnight delivery, common adverse effects cheap 200mg aciclovir free shipping, and nursing tions for use order 200 mg aciclovir amex, routes of administration discount 200mg aciclovir with amex, adverse process implications. Sinatro, a 56-year-old housewife, experiences chest pressure after exercise. She is the mother of six and works 30 hours a week word-processing documents for a law ﬁrm. When she is told that her chest dis- comfort is probably secondary to coronary artery disease, she cannot believe it. Sinatro is referred to her primary care health care provider and given sublingual nitroglycerin tablets to use PRN for chest pain. What lifestyle modiﬁcations would help minimize the progression of coronary artery disease? OVERVIEW according to the amount of physical activity they can tolerate before anginal pain occurs (Box 53–2). These categories can Angina pectoris is a clinical syndrome characterized by assist in clinical assessment and evaluation of therapy. It occurs when there is a deficit in Classic anginal pain is usually described as substernal myocardial oxygen supply (myocardial ischemia) in relation chest pain of a constricting, squeezing, or suffocating nature. It is most often caused by It may radiate to the jaw, neck, or shoulder, down the left or atherosclerotic plaque in the coronary arteries but may also both arms, or to the back. The development and pro- taken for arthritis, or for indigestion, as the pain may be asso- gression of atherosclerotic plaque is called coronary artery ciated with nausea, vomiting, dizziness, diaphoresis, shortness disease (CAD). Atherosclerotic plaque narrows the lumen, of breath, or fear of impending doom. The discomfort is usu- decreases elasticity, and impairs dilation of coronary arteries. There are three main types of angina: classic adults may have atypical symptoms of CAD and may experi- angina, variant angina, and unstable angina (Box 53–1). The ence silent ischemia that may delay them from seeking pro- Canadian Cardiovascular Society classiﬁes clients with angina fessional help. Individuals with diabetes mellitus may present 774 CHAPTER 53 ANTIANGINAL DRUGS 775 BOX 53–1 TYPES OF ANGINA PECTORIS Classic causes platelets to aggregate at the site of injury, form a throm- Classic angina (also called stable, typical, or exertional angina) bus, and release chemical mediators that cause vasoconstriction occurs when atherosclerotic plaque obstructs coronary arteries and (eg, thromboxane, serotonin, platelet-derived growth factor). The the heart requires more oxygenated blood than the blocked arter- disrupted plaque, thrombus, and vasoconstriction combine to ies can deliver. Chest pain is usually precipitated by situations that obstruct blood ﬂow further in the affected coronary artery. When increase the workload of the heart, such as physical exertion, ex- the plaque injury is mild, blockage of the coronary artery may be posure to cold, and emotional upset. Recurrent episodes of classic intermittent and cause silent myocardial ischemia or episodes of angina usually have the same pattern of onset, duration, and in- anginal pain at rest. Pain is usually relieved by rest, a fast-acting may progress until the coronary artery is completely occluded, preparation of nitroglycerin, or both. The spasms occur most often in practice guidelines for the management of angina, deﬁnes unstable coronary arteries that are already partly blocked by atherosclerotic angina as meeting one or more of the following criteria: plaque. Variant angina usually occurs during rest or with minimal • Anginal pain at rest that usually lasts longer than 20 minutes exercise and often occurs at night. It often occurs at the same time • Recent onset (<2 months) of exertional angina of at least each day. Long-term Canadian Cardiovascular Society Classiﬁcation (CCSC) management includes avoidance of conditions that precipitate va- class III severity sospasm, when possible (eg, exposure to cold, smoking, and emo- • Recent (<2 months) increase in severity as indicated by pro- tional stress), as well as antianginal drugs. Unstable However, myocardial ischemia may also be painless or silent Unstable angina (also called rest, preinfarction, and crescendo in a substantial number of clients. Overall, the diagnosis is usu- angina) is a type of myocardial ischemia that falls between classic ally based on chest pain history, electrocardiographic evidence of angina and myocardial infarction. It usually occurs in clients with ischemia, and other signs of impaired cardiac function (eg, heart advanced coronary atherosclerosis and produces increased fre- failure). It often leads to Because unstable angina often occurs hours or days before myocardial infarction. The resulting injury to the endothelium farction, heart failure, or sudden cardiac death.