Pharmacological Management of Cholera: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Cholera is a potentially lethal diarrheal disease produced by Vibrio cholerae serotypes O1 El Tor and O139. Known since antiquity, the condition causes epidemics in many areas, particularly in Asia, Africa, and South America. Left untreated, the mortality may reach 50%. The crucial therapeutic intervention is intravenous or oral rehydration and correction of acidosis, dyselectrolytemia, and renal impairment. Antibiotic use represents the main pharmacological intervention. STUDY QUESTION: What are the milestones of the antibiotics use recommended by experts for the pharmacological management of cholera in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of cholera and particularly the use of antibiotics as presented in a widely used textbook in the United States. DATA SOURCES: The chapters describing the management of cholera in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: Sulfonamides were recommended in 1947, followed by the introduction of tetracyclines, chloramphenicol, and furazolidone in 1955. The options were restricted in 2000 to doxycycline. In the past decade, patients infected with strains known to have a degree a resistance to tetracyclines were treated with azithromycin or ciprofloxacin. Antibiotic use decreases the volume of stool and the duration of diarrhea but has not been considered lifesaving. Drugs with antimotility, antiemetic, or antisecretory properties are not useful. CONCLUSIONS: The utility of antibiotic use in cholera has been endorsed by experts, but only as an adjunct to rapid and complete fluid and electrolyte replacement.

Bed Rest After Acute Myocardial Infarction: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Complete bed rest has been a component of the management of acute myocardial infarction, which was first diagnosed in the United States in 1912. The prescribed duration of bed rest has been progressively shortened in the past century. STUDY QUESTION: What are the milestones of the changes in the expert approach to the duration of bed rest for patients with acute myocardial infarction? STUDY DESIGN: To determine the changes in the experts' approach to the duration of bed rest after a diagnosis of acute myocardial infarction, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters presenting the management of myocardial infarction in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: Complete rest for 2-6 weeks was recommended by the Cecil's experts from 1927 through 1967. The practice was questioned since the early 1950s, but the recommended duration of bed rest was decreased to 3-4 days only in 1971, after most US hospitals opened coronary care units. The required time in bed was further decreased to 1 day in 1992 and to 12 hours in 2004. By 2007, the literature contained data from 15 trials with a total of 1471 patients kept in bed "longer" and 1487 patients who had been prescribed bed rest for "shorter" periods after an acute uncomplicate myocardial infarction and there was no difference between the groups regarding reinfarction, cardiac mortality, or all-cause mortality. CONCLUSIONS: The duration of bed rest after acute myocardial infarction recommended by experts in the United States has had a downward trend with an inflection point in the early 1970s. The change reflected experts' opinion, rather than evidence produced by randomized controlled trials.

Drug-drug interactions involving combinations of antipsychotic agents with antidiabetic, lipid-lowering, and weight loss drugs.

INTRODUCTION: Patients with severe mental illness (SMI) have a high risk for diabetes, dyslipidemia, and other components of metabolic syndrome. Patients with these metabolic comorbidities and cardiac risk factors should receive not only antipsychotics but also medications aiming to reduce cardiovascular risk. Therefore, many patients may be exposed to clinically relevant drug-drug interactions. AREAS COVERED: This narrative review summarizes data regarding the known or potential drug-drug interactions between antipsychotics and medications treating metabolic syndrome components, except for hypertension, which has been summarized elsewhere. A literature search in PubMed and Scopus up to 7/31/2021 was performed regarding interactions between antipsychotics and drugs used to treat metabolic syndrome components, aiming to inform clinicians' choice of medication for patients with SMI and cardiometabolic risk factors in need of pharmacologic interventions. EXPERT OPINION: The cytochrome P450 system and, to a lesser extent, the P-glycoprotein transporter is involved in the pharmacokinetic interactions between antipsychotics and some statins or saxagliptin. Regarding pharmacodynamic interactions, the available information is based mostly on small studies, and for newer classes, like PCSK9 inhibitors or SGLT2 inhibitors, data are still lacking. However, there is sufficient information to guide clinicians in the process of selecting safer antipsychotic-cardiometabolic risk reduction drug combinations.

Pharmacological Management of Pulmonary Tuberculosis: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Advances in drug therapy for pulmonary tuberculosis have had an extraordinary impact on the incidence of tuberculosis in the United States in the past century, which has decreased from 113/100,000 persons in 1920 to 2.2/100,000 in 2020. Modern treatments have contributed to a remarkable decrease in hospitalizations and mortality and have had a significant impact on the duration and severity of illness, quality of life, and work potential of affected persons. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of pulmonary tuberculosis in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of pulmonary tuberculosis, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters describing the management of pulmonary tuberculosis in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: In the preantibiotic era (1927-1943), the Cecil authors emphasized rest, good food, and fresh air as the treatment pillars for pulmonary tuberculosis. The modern era (1947-1971) recorded the discovery of all the drugs that are still used for the initial treatment, in the following order: streptomycin, para-aminosalicylic acid, isoniazid, pyrazinamide, ethambutol, cycloserine, kanamycin, ethionamide, capreomycin, and rifampin. In the postmodern era (1975-2020), therapeutic advances continued with trials of many drug combinations aimed at ameliorating the duration of treatment, drug resistance adverse effects, and poor the recent addition of fluoroquinolones, bedaquiline, and clofazimine. CONCLUSIONS: The pharmacological management of tuberculosis has remained archaic until the middle of the 20th century. Fundamental progress occurred in a very short period (1947-1971) and was because of the recognition of the antituberculous effect of many antibiotics and chemotherapy agents. The challenges created by mycobacterial infections resistant to multiple drugs remain and have prompted the addition of new drugs in the past decade.

Pharmacological Management of Inflammatory Bowel Disease: a Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Advances in drug therapy for inflammatory bowel disease (IBD) [Crohn disease and ulcerative colitis (UC)] have contributed to a decrease in the severity of these chronic and disabling conditions. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of IBD in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of regional ileitis and UC, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters presenting the management of IBD in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: No specific interventions existed from 1927 through 1942. The pharmacological management of IBD has had 3 slightly overlapping eras starting in 1943. During the first period (1943-1951), the medical management relied on antibiotics, primarily sulfonamides and chloramphenicol. In the second (1955-75), experts recommended the use of adrenocorticotropic hormone or corticosteroids and 5-aminosalicylate. In the third era, which commenced in 1979 and is continuing to date, the pharmacological interventions have been expanded and refined to include 5 main drug classes, 5-aminosalicylates (sulfasalazine, mesalamine, and olsalazine), corticosteroids (prednisone and budesonide), immunomodulators (azathioprine, 6-mercaptopurine, cyclosporine, and tofacitinib), biologics (infliximab adalimumab certolizumab pegol, and natalizumab), and antibiotics (metronidazole and ciprofloxacin). A consensus exists that the monoclonal antibodies again tumor necrosis factor alpha are cost-effective for induction and maintenance of clinical remission in both UC (golimumab) and Crohn disease (certolizumab pegol). The newer agents ustekinumab (a monoclonal antibody to the interleukin p40 subunit) and vedolizumab (a monoclonal antibody to the homing receptor integrin complex) have also performed well. CONCLUSIONS: The pharmacological management of IBD has been the focus of intense research and development in the past 60 years. The pillars of drug treatment have been 5-aminosalicylates and corticosteroids. Recent pharmacological innovations (immunomodulators and biologicals) constitute an encouraging paradigm shift in the treatment of UC and Crohn disease.

Drug-drug interactions involving antipsychotics and antihypertensives.

INTRODUCTION: Antipsychotics represent the mainstay in the treatment of patients diagnosed with major psychiatric disorders. Hypertension, among other components of metabolic syndrome, is a common finding in these patients. For their psychiatric and physical morbidity, many patients receive polypharmacy, exposing them to the risk of clinically relevant drug-drug interactions. AREAS COVERED: This review summarizes the knowledge regarding the known or potential drug-drug interactions between antipsychotics and the main drug classes used in the treatment of hypertension. We aimed to provide the clinician an insight into the pharmacokinetic and pharmacodynamic interactions between these drugs for a better choice of combinations of drugs to treat both the mental illness and cardiovascular risk factors. For this, we performed a literature search in PubMed and Scopus databases, up to 31 July 2021. EXPERT OPINION: The main pharmacokinetic interactions between antipsychotics and antihypertensive drugs involve mainly the cytochrome P450 system. The pharmacodynamic interactions are produced by multiple mechanisms, leading to concurrent binding to the same receptors. The data available regarding drug-drug interactions is mostly based on case reports and small studies and therefore should be interpreted with caution. The current knowledge is sufficiently strong to guide clinicians in selecting safer drug combinations as summarized here.

Prehospital Care of Coronary Artery Disease and Its Major Risk Factors in Geropsychiatric Inpatients.

BACKGROUND: Older adults with serious mental illness have a high prevalence of coronary artery disease and of its major risk factors, that is, arterial hypertension, dyslipidemia, and diabetes mellitus. The prevalence and clinical control of these conditions have not been compared in geropsychiatric inpatients with dementia versus those with mood or psychotic disorders. STUDY QUESTION: What is the prevalence and acuity of coronary artery disease, arterial hypertension, dyslipidemia, and diabetes mellitus among patients with dementia, mood, and psychotic disorders admitted for geropsychiatric care? STUDY DESIGN: Patients 65 years of age or older were identified in a cohort of 1000 patients consecutively admitted over a 3-year period to the geropsychiatric unit of a 200-bed mental health hospital in suburban New York. All patients had a structured clinical and laboratory evaluation within 72 hours of admission. DATA SOURCES: Primary psychiatric diagnoses, medical history, the frequency of poorly controlled cardiometabolic comorbidity requiring an immediate change in the management plan, and the Charlson Comorbidity Index (CCI). RESULTS: The 65 years and older patient sample (N = 689) had a mean age of 74.8 years, and 58.8% of the subjects were women. The 205 patients with dementia were older ( P < 0.001) than the 337 patients with mood disorders and the 147 patients with psychotic syndromes. The numbers of medical conditions and the CCI after exclusion of dementia were similar in patients with dementia versus patients without dementia. A substantial number of patients had poorly controlled arterial hypertension (51.2%), dyslipidemia (25.4%), diabetes (24.2%), and coronary artery disease (15.4%). Patients with dementia had a lower prevalence of poorly controlled dyslipidemia ( P = 0.0006), diabetes ( P = 0.0089), and coronary artery disease ( P = 0.045). CONCLUSIONS: Compared with mood or psychotic disorder, a diagnosis of dementia with behavioral disturbance seemed to be associated with better control of coronary artery disease, dyslipidemia, and diabetes mellitus in geropsychiatric inpatients.

Pharmacological Management of Obesity: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Innovations in drug therapy for obesity have had a limited impact on the body mass index, prevalence of medical complications, quality of life, and work potential of a substantial majority of affected persons. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of obesity in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of obesity, as presented in a widely used textbook in the United States. DATA SOURCES: The primary sources were chapters describing the management of obesity in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. Secondary sources were publications retrieved from Medline that clarified technical issues related to the development, regulatory approval, and use of the drugs mentioned in the Cecil Textbook of Medicine. RESULTS: Pharmacological interventions aimed at increasing caloric expenditures through thermogenesis were recommended from 1927 through 1943. Thyroid extracts were prescribed even in the absence of demonstrated hypothyroidism or decreased basal metabolic rate throughout this period. Dinitrophenol was mentioned in 1937, but was banned soon thereafter. Appetite suppression with amphetamine was considered useful from 1943 through 1988, after which the drug was replaced with other centrally acting molecules, such as fenfluramine in 1988, sibutramine in 2000, and rimonabant in 2008, which were in turn withdrawn because of major adverse effects. In the past decade, obesity has been treated with the appetite suppressants phentermine-topiramate, bupropion-naltrexone, lorcaserin, and liraglutide, and with orlistat, a drug promoting fat malabsorption. The change in weight produced by these drugs is generally modest and transient. CONCLUSIONS: The pharmacological management of obesity has remained frustratingly inefficient. The reasons for the relative lack of success may reside in the ever-growing access to dense, palatable, and relatively inexpensive food, coupled with the decrease in energy expenditure created by a sedentary lifestyle.

Pharmacological Management of Primary Arterial Hypertension: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Advances in drug therapy for primary (or essential) arterial hypertension have contributed to a significant decrease in the frequency and severity of strokes, coronary artery disease and heart failure, and chronic renal insufficiency. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of arterial hypertension in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of arterial hypertension, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters presenting the management of arterial hypertension in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: The pharmacological management of arterial hypertension has had 3 overlapping eras in the timeframe subject to our investigation. In the empiric era (1927-1947), experts were recommending nonspecific interventions for sedation. The premodern era (1955-1963) relied on ganglion blockers, sympathetic blockers, and direct vasodilators. The modern era (1967-2020), which includes drugs used in current clinical practice, saw the introduction of diuretics (1967), beta-blockers (1971), alpha-blockers (1982), calcium channel blockers (1985), angiotensin-converting enzyme inhibitors (1985), angiotensin receptor blockers (2000), and direct renin inhibitors (2008). CONCLUSIONS: The pharmacological management of arterial hypertension has been the focus of intense and successful research and development in the second half of the 20th century.

Pharmacological Management of Heroin Withdrawal Syndrome: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Opioid use disorder continues to have a significant impact on public health morbidity and mortality throughout the United States and elsewhere. Managing opioid withdrawal is a critical treatment goal in individuals entering treatment with an active opioid use. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of heroin withdrawal syndrome in the past century? STUDY DESIGN: To determine the changes in the expert approach to the management of heroin withdrawal syndrome, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters on opioid dependence in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: Opioid replacement taper with morphine (1927-1947), codeine (1931-1943), and methadone (1951-present) administered for 3-10 days has remained the main intervention. The anticholinergic drugs, scopolamine and atropine, were recommended from 1927 to 1943, but their use has never been backed by scientific evidence. Newer approaches relied on clonidine, an alpha-2 receptor agonist used since 1982, and buprenorphine, an opioid agonist/antagonist endorsed for the treatment of heroin withdrawal in 2000. CONCLUSIONS: The pharmacological management of heroin withdrawal syndrome in the past century has progressed from the introduction of methadone to the utilization of clonidine and buprenorphine. More recent advances in treating opioid use disorder have changed the goals of opioid withdrawal management to achievement of abstinence from all opioids to facilitation of long-term treatment with medications for opioid use disorder.