Preventive healthcare consists of measures taken for disease prevention, as opposed to disease treatment. Just as health comprises a variety of physical and mental states, so do disease and disability, which are affected by environmental factors, genetic predisposition, disease agents, lifestyle choices. Health and disability are dynamic processes which begin before individuals realize they are affected. Disease prevention relies on anticipatory actions that can be categorized as primal, primary and tertiary prevention; each year, millions of people die of preventable deaths. A 2004 study showed that about half of all deaths in the United States in 2000 were due to preventable behaviors and exposures. Leading causes included cardiovascular disease, chronic respiratory disease, unintentional injuries and certain infectious diseases; this same study estimates that 400,000 people die each year in the United States due to poor diet and a sedentary lifestyle. According to estimates made by the World Health Organization, about 55 million people died worldwide in 2011, two thirds of this group from non-communicable diseases, including cancer and chronic cardiovascular and lung diseases.
This is an increase from the year 2000, during which 60% of deaths were attributed to these diseases. Preventive healthcare is important given the worldwide rise in prevalence of chronic diseases and deaths from these diseases. There are many methods for prevention of disease, it is recommended that adults and children aim to visit their doctor for regular check-ups if they feel healthy, to perform disease screening, identify risk factors for disease, discuss tips for a healthy and balanced lifestyle, stay up to date with immunizations and boosters, maintain a good relationship with a healthcare provider. Some common disease screenings include checking for hypertension, hypercholesterolemia, screening for colon cancer, depression, HIV and other common types of sexually transmitted disease such as chlamydia and gonorrhea, colorectal cancer screening, a Pap test, screening for osteoporosis. Genetic testing can be performed to screen for mutations that cause genetic disorders or predisposition to certain diseases such as breast or ovarian cancer.
However, these measures are not affordable for every individual and the cost effectiveness of preventive healthcare is still a topic of debate. Preventive healthcare strategies are described as taking place at the primal, primary and tertiary prevention levels. In the 1940s, Hugh R. Leavell and E. Gurney Clark coined the term primary prevention, they worked at the Harvard and Columbia University Schools of Public Health and expanded the levels to include secondary and tertiary prevention. Goldston notes that these levels might be better described as "prevention and rehabilitation", though the terms primary and tertiary prevention are still in use today; the concept of primal prevention has been created much more in relation to the new developments in molecular biology over the last fifty years, more in epigenetics, which point to the paramount importance of environmental conditions - both physical and affective - on the organism during its fetal and newborn life. Primal prevention has been propounded as a separate category of "health promotion".
This health promotion par excellence is based on the'new knowledge' in molecular biology, in particular on epigenetic knowledge, which points to how much affective - as well as physical - environment during fetal and newborn life may determine each and every aspect of adult health. This new way of promoting health consists in providing future parents with pertinent, unbiased information on primal health and supporting them during their child's primal period of life; this includes adequate parental leave - ideally for both parents - with kin caregiving and financial help where needed. Another related concept is primordial prevention which refers to all measures designed to prevent the development of risk factors in the first place, early in life. Primary prevention consists of traditional "health promotion" and "specific protection." Health promotion activities are non-clinical life choices. For example, eating nutritious meals and exercising daily, that both prevent disease and create a sense of overall well-being.
Preventing disease and creating overall well-being, prolongs our life expectancy. Health-promotional activities do not target a specific disease or condition but rather promote health and well-being on a general level. On the other hand, specific protection targets a type or group of diseases and complements the goals of health promotion. Food is much the most basic tool in preventive health care; the 2011 National Health Interview Survey performed by the Centers for Disease Control was the first national survey to include questions about ability to pay for food. Difficulty with paying for food, medicine, or both is a problem facing 1 out of 3 Americans. If better food options were available through food banks, soup kitchens, other resources for low-income people and the chronic conditions that come along with it would be better controlled A "food desert" is an area with restricted access to healthy foods due to a lack of supermarkets within a reasonable distance; these are ofte
A diuretic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine. In medicine, diuretics are used to treat heart failure, liver cirrhosis, influenza, water poisoning, certain kidney diseases; some diuretics, such as acetazolamide, help to make the urine more alkaline and are helpful in increasing excretion of substances such as aspirin in cases of overdose or poisoning. Diuretics are sometimes abused by people with an eating disorder people with bulimia nervosa, with the goal of losing weight; the antihypertensive actions of some diuretics are independent of their diuretic effect. That is, the reduction in blood pressure is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis.
Indapamide was designed with this in mind, has a larger therapeutic window for hypertension than most other diuretics. High ceiling diuretics may cause a substantial diuresis – up to 20% of the filtered load of NaCl and water; this is large in comparison to normal renal sodium reabsorption which leaves only about 0.4% of filtered sodium in the urine. Loop diuretics have this ability, are therefore synonymous with high ceiling diuretics. Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb sodium at the ascending loop in the nephron, which leads to an excretion of water in the urine, whereas water follows sodium back into the extracellular fluid. Other examples of high ceiling loop diuretics include ethacrynic torasemide. Thiazide-type diuretics such as hydrochlorothiazide act on the distal convoluted tubule and inhibit the sodium-chloride symporter leading to a retention of water in the urine, as water follows penetrating solutes. Frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule.
The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure. On the other hand, the long-term effect is due to an unknown vasodilator effect that decreases blood pressure by decreasing resistance. Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase, found in the proximal convoluted tubule; this results in several effects including bicarbonate accumulation in the urine and decreased sodium absorption. Drugs in this class include methazolamide; these are diuretics. The term "potassium-sparing" refers to an effect rather than a location. Aldosterone adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption. Similar agents are potassium canreonate. Epithelial sodium channel blockers: amiloride and triamterene; the term "calcium-sparing diuretic" is sometimes used to identify agents that result in a low rate of excretion of calcium.
The reduced concentration of calcium in the urine can lead to an increased rate of calcium in serum. The sparing effect on calcium can be beneficial in unwanted in hypercalcemia; the thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics. The thiazides cause a net decrease in calcium lost in urine; the potassium-sparing diuretics cause a net increase in calcium lost in urine, but the increase is much smaller than the increase associated with other diuretic classes. By contrast, loop diuretics promote a significant increase in calcium excretion; this can increase risk of reduced bone density. Osmotic diuretics are substances that increase osmolarity but have limited tubular epithelial cell permeability, they work by expanding extracellular fluid and plasma volume, therefore increasing blood flow to the kidney the peritubular capillaries. This thus impairs the concentration of urine in the loop of Henle. Furthermore, the limited tubular epithelial cell permeability increases osmolality and thus water retention in the filtrate.
It was believed that the primary mechanism of osmotic diuretics such as mannitol is that they are filtered in the glomerulus, but cannot be reabsorbed. Thus their presence leads to an increase in the osmolarity of the filtrate and to maintain osmotic balance, water is retained in the urine. Glucose, like mannitol, is a sugar that can behave as an osmotic diuretic. Unlike mannitol, glucose is found in the blood. However, in certain conditions, such as diabetes mellitus, the concentration of glucose in the blood exceeds the maximum reabsorption capacity of the kidney; when this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Glucosuria causes a loss of hypotonic water and Na+, leading to a hypertonic state wit
Direct Xa inhibitor
Direct factor Xa inhibitors are a class of anticoagulant drugs which act directly upon Factor X in the coagulation cascade, without using antithrombin as a mediator. Direct factor Xa inhibitors are being used clinically. Clinical trials have shown promise for these compounds as substitutes for the administered vitamin K antagonists or low molecular weight heparin; those trials demonstrated efficacy and safety against warfarin for stroke prevention in atrial fibrillation and against low-molecular-weight heparin for treatment and secondary prevention of venous thromboembolism or for initial treatment and prevention of venous thromboembolism in patients undergoing hip or knee replacement. Advantages of orally administered direct Xa inhibitors lie in the fact that they have a rapid onset and offset of action which reduces need for "bridging" with a parenteral anticoagulant, that they don't require frequent monitoring or re-dosing whilst having few strong drug interactions and no food interactions, leading to greater convenience by patients and doctors and that they have a lower risk of intra cranial bleeding in trials.
Disadvantages compared to warfarin include the limited prospective experience, concerns regarding patient adherence without laboratory monitoring, uncertainty about dosing in some patient populations, their contraindication in severe renal impairment, their lack of specific antidotes and assays to measure drug levels in case of severe bleeding, their potential to overuse in low risk atrial fibrillation people, their short half live affecting efficacy and their higher drug acquisition costs. A new series of oral, direct-acting inhibitors of Factor Xa have entered clinical development, are competitors of dabigatran, a direct thrombin inhibitor; these include rivaroxaban from Janssen, apixaban from Bristol-Myers Squibb, betrixaban from Portola Pharmaceuticals, darexaban from Astellas, edoxaban from Daiichi, otamixaban by Sanofi, more letaxaban from Takeda and eribaxaban from Pfizer. The development of darexaban was discontinued in September 2011: in a trial for prevention of recurrences of myocardial infarction in top of dual anti platelet therapy, the drug didn't work and the risk for bleeding was increased by 300%.
Andexanet alfa, a specific antidote to reverse the anticoagulant activity of direct Xa inhibitors in the event of major bleeding, was approved by the FDA in 2018. There is limited clinical experience with the medication. There is some limited evidence supporting use of non-specific prohemostatic therapies such as prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant factor VIIa. A occurring inhibitor of factor Xa was first reported in 1971 by Spellman et al. from the dog hookworm. In 1987, Tuszynski et al. discovered antistasin, isolated from the extracts of Mexican leech, Haementeria officinalis. Soon after this, another occurring inhibitor, tick anticoagulant peptide was isolated from the extract of tick Ornithodoros moubata. Spellman, GG Jr.. "Anticoagulant activity of dog hookworm". Am J Physiol. 222: 922–27. Doi:10.1152/ajplegacy.19184.108.40.2062. PMID 5102508. Direct Factor Xa Inhibitors as Anticoagulants | PharmaXChange.info – A review and presentation on the available factor Xa inhibitors which can be used as anticoagulants.
Oral Xa inhibitors – Literature review of the evidence regarding oral Xa inhibitors http://ajplegacy.physiology.org/content/220/4/922.full-text.pdf+html
Calcium channel blocker
Calcium channel blockers, calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e. as medications to decrease blood pressure in patients with hypertension. CCBs are effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are frequently used to alter heart rate, to prevent peripheral and cerebral vasospasm, to reduce chest pain caused by angina pectoris. N-type, L-type, T-type voltage-dependent calcium channels are present in the zona glomerulosa of the human adrenal gland, CCBs can directly influence the biosynthesis of aldosterone in adrenocortical cells, with consequent impact on the clinical treatment of hypertension with these agents. CCBs have been shown to be more effective than beta blockers at lowering cardiovascular mortality, but they are associated with more side effects.
Potential major risks however were found to be associated with short-acting CCBs. Dihydropyridine calcium channel blockers are derived from the molecule dihydropyridine and used to reduce systemic vascular resistance and arterial pressure. Sometimes when they are used to treat angina, the vasodilation and hypotension can lead to reflex tachycardia, which can be detrimental for patients with ischemic symptoms because of the resulting increase in myocardial oxygen demand. Dihydropyridine calcium channel blockers can worsen proteinuria in patients with nephropathy; this CCB class is identified by the suffix "-dipine". Amlodipine Aranidipine Azelnidipine Barnidipine Benidipine Cilnidipine Not available in US Clevidipine Efonidipine Felodipine Isradipine Lacidipine Lercanidipine Manidipine Nicardipine Nifedipine Nilvadipine Nimodipine This substance can pass the blood-brain barrier and is used to prevent cerebral vasospasm. Nisoldipine Nitrendipine Pranidipine Phenylalkylamine calcium channel blockers are selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, are used to treat angina.
They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less reflex tachycardia, making it appealing for treatment of angina, where tachycardia can be the most significant contributor to the heart's need for oxygen. Therefore, as vasodilation is minimal with the phenylalkylamines, the major mechanism of action is causing negative inotropy. Phenylalkylamines are thought to access calcium channels from the intracellular side, although the evidence is somewhat mixed. Fendiline Gallopamil Verapamil Benzothiazepine calcium channel blockers belong to the benzothiazepine class of compounds and are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines. Diltiazem While most of the agents listed above are selective, there are additional agents that are considered nonselective.
These include mibefradil, flunarizine and fendiline. Gabapentinoids, such as gabapentin and pregabalin, are selective blockers of α2δ subunit-containing voltage-gated calcium channels, they are used to treat epilepsy and neuropathic pain. Ziconotide, a peptide compound derived from the omega-conotoxin, is a selective N-type calcium channel blocker that has potent analgesic properties that are equivalent to approximate 1,000 times that of morphine, it must be delivered via the intrathecal route via an intrathecal infusion pump. Side effects of these drugs may include but are not limited to: Constipation Dizziness, redness in the face Fluid buildup in the legs and ankle edema Gingival overgrowth Rapid heart rate Slow heart rate Research indicates ethanol is involved in the inhibition of L-type calcium channels. One study showed the nature of ethanol binding to L-type calcium channels is according to first-order kinetics with a Hill coefficient around 1; this indicates ethanol binds independently to the channel.
Early studies showed a link between calcium and the release of vasopressin by the secondary messenger system. Vasopressin levels are reduced after the ingestion of alcohol; the lower levels of vasopressin from the consumption of alcohol have been linked to ethanol acting as an antagonist to voltage-gated calcium channels. Studies conducted by Treistman et al. in the aplysia confirm inhibition of VGCC by ethanol. Voltage clamp recordings have been done on the aplysia neuron. VGCCs were isolated and calcium current was recorded using patch clamp technique having ethanol as a treatment. Recordings were replicated at varying concentrations at a voltage clamp of +30 mV. Results showed. Similar results have shown to be true in single-channel recordings from isolated nerve terminal of rats that ethanol does in fact block VGCCs. Studies done by Katsura et al. in 2006 on mouse cerebral cortical neurons, show the effects of prolonged ethanol
Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, reduce the likelihood of dementia, heart failure, mortality from cardiovascular disease. There are many classes of antihypertensives. Among the most important and most used drugs are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists, beta blockers. Which type of medication to use for hypertension has been the subject of several large studies and resulting national guidelines; the fundamental goal of treatment should be the prevention of the important endpoints of hypertension, such as heart attack and heart failure. Patient age, associated clinical conditions and end-organ damage play a part in determining dosage and type of medication administered.
The several classes of antihypertensives differ in side effect profiles, ability to prevent endpoints, cost. The choice of more expensive agents, where cheaper ones would be effective, may have negative impacts on national healthcare budgets; as of 2018, the best available evidence favors low-dose thiazide diuretics as the first-line treatment of choice for high blood pressure when drugs are necessary. Although clinical evidence shows calcium channel blockers and thiazide-type diuretics are preferred first-line treatments for most people, an ACE inhibitor is recommended by NICE in the UK for those under 55 years old. Diuretics help the kidneys eliminate excess water from the body's tissues and blood. Loop diuretics: bumetanide ethacrynic acid furosemide torsemide Thiazide diuretics: epitizide hydrochlorothiazide and chlorothiazide bendroflumethiazide methyclothiazide polythiazide Thiazide-like diuretics: indapamide chlorthalidone metalozone Xipamide Clopamide Potassium-sparing diuretics: amiloride triamterene spironolactone eplerenoneIn the United States, the JNC8 recommends thiazide-type diuretics to be one of the first-line drug treatments for hypertension, either as monotherapy or in combination with calcium channel blockers, ACE inhibitors, or angiotensin II receptor antagonists.
There are fixed-dose combination drugs, such as ACE thiazide combinations. Despite thiazides being cheap and effective, they are not prescribed as as some newer drugs; this is because they have been associated with increased risk of new-onset diabetes and as such are recommended for use in patients over 65 where the risk of new-onset diabetes is outweighed by the benefits of controlling systolic blood pressure. Another theory is that they are off-patent and thus promoted by the drug industry. Calcium channel blockers block the entry of calcium into muscle cells in artery walls. Dihydropyridines: amlodipine cilnidipine clevidipine felodipine isradipine lercanidipine levamlodipine nicardipine nifedipine nimodipine nisoldipine nitrendipine non-dihydropyridines: diltiazem verapamilJNC8 recommends calcium channel blockers to be a first-line treatment either as monotherapy or in combination with thiazide-type diuretics, ACE inhibitors, or angiotensin II receptor antagonists for all patients regardless of age or race.
The ratio of CCBs' anti-proteinuria effect, non-dihydropyridine to dihydropyridine was 30 to -2. ACE inhibitors inhibit the activity of angiotensin-converting enzyme, an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor. Captopril enalapril fosinopril lisinopril moexipril perindopril quinapril ramipril trandolapril benazeprilA systematic review of 63 trials with over 35,000 participants indicated ACE inhibitors reduced doubling of serum creatinine levels compared to other drugs, the authors suggested this as a first line of defense; the AASK trial showed that ACE inhibitors are more effective at slowing down the decline of kidney function compared to calcium channel blockers and beta blockers. As such, ACE inhibitors should be the drug treatment of choice for patients with chronic kidney disease regardless of race or diabetic status. However, ACE inhibitors should not be a first-line treatment for black hypertensives without chronic kidney disease.
Results from the ALLHAT trial showed that thiazide-type diuretics and calcium channel blockers were both more effective as monotherapy in improving cardiovascular outcomes compared to ACE inhibitors for this subgroup. Furthermore, ACE inhibitors were less effective in reducing blood pressure and had a 51% higher risk of stroke in black hypertensives when used as initial therapy compared to a calcium channel blocker. There are fixed-dose combination drugs, such as ACE thiazide combinations. Notable side effects of ACE inhibitors include dry cough, fatigue, headaches, loss of taste and a risk for angioedema. Angiotensin II receptor antagonists work by antagonizing the activation of angiotensin receptors. Azilsartan candesartan eprosartan irbesartan losartan olmesartan telmisartan valsartan FimasartanIn 2004, an article in the BMJ examined the evidence for and against the suggestion that angiotensin receptor blockers may increase the risk of myocardial infarction; the matter was debated in 2006 in the medical journal of the American Heart Association.
To date, there is no consensus on whether ARBs have a tendenc
Metabolism is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of food to energy to run cellular processes; these enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, respond to their environments.. Metabolic reactions may be categorized as catabolic - the breaking down of compounds. Catabolism releases energy, anabolism consumes energy; the chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, each step being facilitated by a specific enzyme. Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy that will not occur by themselves, by coupling them to spontaneous reactions that release energy. Enzymes act as catalysts - they allow a reaction to proceed more - and they allow the regulation of the rate of a metabolic reaction, for example in response to changes in the cell's environment or to signals from other cells.
The metabolic system of a particular organism determines which substances it will find nutritious and which poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals; the basal metabolic rate of an organism is the measure of the amount of energy consumed by all of these chemical reactions. A striking feature of metabolism is the similarity of the basic metabolic pathways among vastly different species. For example, the set of carboxylic acids that are best known as the intermediates in the citric acid cycle are present in all known organisms, being found in species as diverse as the unicellular bacterium Escherichia coli and huge multicellular organisms like elephants; these similarities in metabolic pathways are due to their early appearance in evolutionary history, their retention because of their efficacy. Most of the structures that make up animals and microbes are made from three basic classes of molecule: amino acids and lipids; as these molecules are vital for life, metabolic reactions either focus on making these molecules during the construction of cells and tissues, or by breaking them down and using them as a source of energy, by their digestion.
These biochemicals can be joined together to make polymers such as DNA and proteins, essential macromolecules of life. Proteins are made of amino acids arranged in a linear chain joined together by peptide bonds. Many proteins are enzymes. Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, a system of scaffolding that maintains the cell shape. Proteins are important in cell signaling, immune responses, cell adhesion, active transport across membranes, the cell cycle. Amino acids contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress. Lipids are the most diverse group of biochemicals, their main structural uses are as part of biological membranes both internal and external, such as the cell membrane, or as a source of energy. Lipids are defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as benzene or chloroform.
The fats are a large group of compounds that contain fatty glycerol. Several variations on this basic structure exist, including alternate backbones such as sphingosine in the sphingolipids, hydrophilic groups such as phosphate as in phospholipids. Steroids such as cholesterol are another major class of lipids. Carbohydrates are aldehydes or ketones, with many hydroxyl groups attached, that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, fill numerous roles, such as the storage and transport of energy and structural components; the basic carbohydrate units are called monosaccharides and include galactose and most glucose. Monosaccharides can be linked together to form polysaccharides in limitless ways; the two nucleic acids, DNA and RNA, are polymers of nucleotides. Each nucleotide is composed of a phosphate attached to a ribose or deoxyribose sugar group, attached to a nitrogenous base. Nucleic acids are critical for the storage and use of genetic information, its interpretation through the processes of transcription and protein biosynthesis.
This information is propagated through DNA replication. Many viruses have an RNA genome, such as HIV, which uses reverse transcription to create a DNA template from its viral RNA genome. RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made