1.
Drug nomenclature
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Drug nomenclature is the systematic naming of drugs, especially pharmaceutical drugs. Generic names for drugs are nowadays constructed out of affixes and stems that classify the drugs into different categories, a marketed drug might also have a company code or compound code. The chemical names are the names, based on the molecular structure of the drug. There are various systems of nomenclature and thus various chemical names for any one substance. The most important is the IUPAC name, chemical names are typically very long and too complex to be commonly used in referring to a drug. Sometimes, a company that is developing a drug might give the drug a company code, for example, CDP870 is UCB’s company code for Cimzia. Many of these codes, although not all, have prefixes that correspond to the company name, during development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, and it will apply for a generic name for that country. It will also apply for an International Nonproprietary Name through the World Health Organization, nowadays the national nonproprietary names are usually the same as the INN. The generic names usually indicate via their stems what drug class the drug belongs to, for example, one can tell that aciclovir is an antiviral drug because its name ends in the -vir suffix. Otherwise the 2 names are both given, joined by hyphens or slashes. For example, suspensions combining trimethoprim and sulfamethoxazole are called either trimethoprim/sulfamethoxazole or co-trimoxazole, similarly, co-codamol is codeine-acetaminophen, and co-triamterzide is triamterene-hydrochlorothiazide. The USP ceased maintaining PENs, but the similar co-prefixed BANs are still current, for drugs that make it all the way through development, testing, and regulatory acceptance, the pharmaceutical company then gives the drug a trade name. The term trade name is a term in the pharmaceutical industry for a brand name or trademark name. For example, Lipitor is Pfizers trade name for atorvastatin, a cholesterol-lowering medication, Drug names are often subject to legal regulation, including approval for new drugs and on packaging to establish clear rules about adulterants and fraudulent or misleading labelling. A national formulary is often designated to define drug names for regulatory purposes, unbiased mentions of a drug place the nonproprietary name first and follow it with the trade name in parentheses, if relevant. This pattern is important for the literature, where conflict of interest is disclosed or avoided. The authors reporting on a study are not endorsing any particular brand of drug and they will often state which brand was used, for methodologic validity, but they do so in a way that makes clear the absence of endorsement. For example, the 2015 American Society of Hematology publication policies say, Non-proprietary names should be used and he first letter of the name of a proprietary drug should be capitalized
2.
Intramuscular injection
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Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of alternative methods for the administration of medications. Muscles have larger and more vessels than subcutaneous tissue and injections here usually have faster rates of absorption than subcutaneous injections or intradermal injections. Depending on the site, an administration is limited to between 2 and 5 milliliters of fluid. Platelet-rich plasma injections can be administered intramuscularly, certain substances are injected intramuscularly for recreational purposes. Possible sites for IM injection include, deltoid, dorsogluteal, rectus femoris, vastus lateralis, sites that are bruised, tender, red, swollen, inflamed or scarred are avoided. The deltoid muscle site is recommended for use with injections of small volume, usually equal or less than 1 ml and this site is not recommended for repeated injections, due to its small area, it is difficult to rotate the injection site. To locate the site, palpate the lower edge of the acromion process, inject in the upside down triangle that forms with its base at the acromion process and its midpoint in line with the axilla. The ventrogluteal site is recommended for injections requiring a larger volume to be administered, greater than 1 ml and it is also given for narcotic, antibiotic, sedative and anti-emetic medications. To locate the site, place the palm of your hand over the greater trochanter. The right hand is used for the hip and left hand is used for the right hip. Place the index finger on the superior iliac spine and run the middle finger back along the iliac crest. The injection is given in the center of the triangle that is formed, the vastus lateralis site is the recommended site for infants less than 7 months old and those unable to walk, with loss of muscular tone. To locate the site, divide the front thigh into thirds vertically and horizontally to make nine squares and inject in the outer middle square. Use of this site is associated with skin and tissue trauma, muscle fibrosis and contracture, haematoma, nerve palsy and paralysis, as well as infectious processes such as abscess and gangrene. The injection site is located by dividing the buttock into four with a plus shaped cross, the selected site is cleansed with an antimicrobial and is allowed to dry. It is injected with the dominant hand using a quick, darting motion perpendicular to the body at an angle between 72 and 90 degrees, as a faster injection is less painful. The needle is then stabilized with the nondominant hand while the dominant hand slides to the plunger to slowly instill the medication, the CDC does not recommend the outdated practice of aspirating for blood to rule out injecting into a blood vessel
3.
Subcutaneous injection
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A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the cutis. Subcutaneous injections are highly effective in administering vaccines and medications such as insulin, morphine, diacetylmorphine, subcutaneous, as opposed to intravenous, injection of recreational drugs is referred to as skin popping. Subcutaneous administration may be abbreviated as SC, SQ, sub-cu, sub-Q, SubQ, subcut is the preferred abbreviation for patient safety. Subcutaneous tissue has few blood vessels and so drugs injected here are for slow and it is slower than Intramuscular injections but still faster than intradermal injections. Sites include, The outer area of the upper arm, the abdomen, from the rib margin to the iliac crest and avoiding a 2-inch circle around the navel. This has the fastest rate of absorption among the sites, the front of the thigh, midway to the outer side,4 inches below the top of the thigh to 4 inches above the knee. This has a rate of absorption than the upper arm. The upper area of the buttock, just behind the hip bone and this has the slowest rate of absorption among the sites. A25 to 31 gauge thick, 3/8 to 1 long needle can be used, the size is determined by the amount of subcutaneous tissue present, which is based on patient build. The 3/8 and 5/8 needles are most commonly used, usually, no more than 1 mL of solution is given, compared to intradermal injections, where no more than 0.5 mL is usually given. Medication is administered slowly, about 10 seconds/milliliter, a person with insulin dependent diabetes mellitus typically injects insulin subcutaneously. The injection should be given under the skin, into the fat layer
4.
Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc
5.
Pharmacokinetics
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Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Pharmacokinetic properties of chemicals are affected by the route of administration and these may affect the absorption rate. Models have been developed to simplify conceptualization of the processes that take place in the interaction between an organism and a chemical substance. The various compartments that the model is divided into are commonly referred to as the ADME scheme, absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids, metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion - the removal of the substances from the body, in rare cases, some drugs irreversibly accumulate in body tissue. The two phases of metabolism and excretion can also be grouped together under the title elimination, the study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. All these concepts can be represented through mathematical formulas that have a graphical representation. The model outputs for a drug can be used in industry or in the application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals, in practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph, compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model. The final outcome of the transformations that a drug undergoes in an organism, a number of functional models have been developed in order to simplify the study of pharmacokinetics. These models are based on a consideration of an organism as a number of related compartments, the simplest idea is to think of an organism as only one homogenous compartment. However, these models do not always reflect the real situation within an organism
6.
Bioavailability
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By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, its bioavailability generally decreases or may vary from patient to patient, Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration. Bioavailability is defined differently for drugs as opposed to dietary supplements primarily due to the method of administration and Food. Bioaccessibility is a related to bioavailability in the context of biodegradation. A molecule is said to be bioaccessible when is available to cross a cellular membrane from the environment. In pharmacology, bioavailability is a measurement of the rate and extent to which a drug reaches at the site of action and it is denoted by the letter f. Therefore, bioavailability for dietary supplements can be defined as the proportion of the administered substance capable of being absorbed, in both pharmacology and nutrition sciences, bioavailability is measured by calculating the area under curve of the drug concentration time profile. Bioavailability is commonly a factor in the production of crops. Toxic materials in soil, such as lead from paint may be rendered unavailable to animals ingesting contaminated soil by supplying phosphorus fertilizers in excess and it is the fraction of the drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be normalized, consequently, the amount absorbed is corrected by dividing the corresponding dose administered. The absolute bioavailability is the area under curve non-intravenous divided by AUC intravenous. For example, the formula for calculating F for a drug administered by the route is given below. If we compare the two different dosage forms having same active ingredients and compare the two drug bioavailability is called comparative bioavailability, although knowing the true extent of systemic absorption is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is that its assessment requires a reference, that is. These limitations may be overcome, however, by administering a low dose of an isotopically labelled drug concomitantly with a therapeutic non-labelled oral dose. This technique eliminates pharmacokinetic issues on non-equivalent clearance as well as enabling the intravenous dose to be administered with a minimum of toxicology, the technique was first applied using stable-isotopes such as 13C and mass-spectrometry to distinguish the isotopes by mass difference. More recently, 14C labelled drugs are administered intravenously and accelerator mass spectrometry used to measure the isotopically labelled drug along with mass spectrometry for the unlabelled drug, in all such cases, to conduct an absolute bioavailability study requires that the drug be given intravenously. Intravenous administration of a drug can provide valuable information on the fundamental pharmacokinetic parameters of volume of distribution
7.
Drug metabolism
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Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. These pathways are a form of biotransformation present in all groups of organisms. These reactions often act to detoxify poisonous compounds, the study of drug metabolism is called pharmacokinetics. The metabolism of drugs is an important aspect of pharmacology. For example, the rate of metabolism determines the duration and intensity of a drugs pharmacologic action, the enzymes of xenobiotic metabolism, particularly the glutathione S-transferases are also important in agriculture, since they may produce resistance to pesticides and herbicides. Drug metabolism is divided into three phases, in phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified compounds are conjugated to polar compounds in phase II reactions. These reactions are catalysed by enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be processed, before being recognised by efflux transporters. Drug metabolism often converts lipophilic compounds into hydrophilic products that are readily excreted. The exact compounds an organism is exposed to will be unpredictable, and may differ widely over time. The solution that has evolved to address this problem is an elegant combination of physical barriers, all organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. This selective uptake means that most hydrophilic molecules cannot enter cells, in contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, cannot exclude lipid-soluble xenobiotics using membrane barriers. However, the existence of a permeability barrier means that organisms were able to evolve detoxification systems that exploit the hydrophobicity common to membrane-permeable xenobiotics and these systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise almost any non-polar compound. Useful metabolites are excluded since they are polar, and in general one or more charged groups. However, since these compounds are few in number, specific enzymes can recognize, the metabolism of xenobiotics is often divided into three phases, - modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells, in phase I, a variety of enzymes act to introduce reactive and polar groups into their substrates. One of the most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system and these enzyme complexes act to incorporate an atom of oxygen into nonactivated hydrocarbons, which can result in either the introduction of hydroxyl groups or N-, O- and S-dealkylation of substrates
8.
Blood
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Blood is a body fluid in humans and other animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells. In vertebrates, it is composed of blood cells suspended in blood plasma, plasma, which constitutes 55% of blood fluid, is mostly water, and contains dissipated proteins, glucose, mineral ions, hormones, carbon dioxide, and blood cells themselves. Albumin is the protein in plasma, and it functions to regulate the colloidal osmotic pressure of blood. The blood cells are red blood cells, white blood cells. The most abundant cells in blood are red blood cells. These contain hemoglobin, a protein, which facilitates oxygen transport by reversibly binding to this respiratory gas. In contrast, carbon dioxide is mostly transported extracellularly as bicarbonate ion transported in plasma, vertebrate blood is bright red when its hemoglobin is oxygenated and dark red when it is deoxygenated. Some animals, such as crustaceans and mollusks, use hemocyanin to carry oxygen, insects and some mollusks use a fluid called hemolymph instead of blood, the difference being that hemolymph is not contained in a closed circulatory system. In most insects, this blood does not contain oxygen-carrying molecules such as hemoglobin because their bodies are small enough for their system to suffice for supplying oxygen. Jawed vertebrates have an immune system, based largely on white blood cells. White blood cells help to resist infections and parasites, platelets are important in the clotting of blood. Arthropods, using hemolymph, have hemocytes as part of their immune system, Blood is circulated around the body through blood vessels by the pumping action of the heart. Medical terms related to blood often begin with hemo- or hemato- from the Greek word αἷμα for blood. In terms of anatomy and histology, blood is considered a form of connective tissue, given its origin in the bones. The average adult has a volume of roughly 5 litres. These blood cells consist of erythrocytes, leukocytes, and thrombocytes, by volume, the red blood cells constitute about 45% of whole blood, the plasma about 54. 3%, and white cells about 0. 7%. Whole blood exhibits non-Newtonian fluid dynamics, if all human hemoglobin were free in the plasma rather than being contained in RBCs, the circulatory fluid would be too viscous for the cardiovascular system to function effectively. One microliter of blood contains,4.7 to 6.1 million,4.2 to 5.4 million erythrocytes, Red blood cells contain the bloods hemoglobin, mature red blood cells lack a nucleus and organelles in mammals
9.
Tissue (biology)
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In biology, tissue is a cellular organizational level intermediate between cells and a complete organ. A tissue is an ensemble of similar cells from the origin that together carry out a specific function. Organs are then formed by the grouping together of multiple tissues. The study of tissue is known as histology or, in connection with disease, the classical tools for studying tissues are the paraffin block in which tissue is embedded and then sectioned, the histological stain, and the optical microscope. In the last couple of decades, developments in microscopy, immunofluorescence. With these tools, the appearances of tissues can be examined in health and disease. Animal tissues are grouped into four types, connective, muscle, nervous. Collections of tissues joined in structural units to serve a common function compose organs, while all animals can generally be considered to contain the four tissue types, the manifestation of these tissues can differ depending on the type of organism. For example, the origin of the cells comprising a particular type may differ developmentally for different classifications of animals. By contrast, a true epithelial tissue is present only in a layer of cells held together via occluding junctions called tight junctions. This tissue covers all surfaces that come in contact with the external environment such as the skin, the airways. It serves functions of protection, secretion, and absorption, and is separated from other tissues below by a basal lamina and they are made up of cells separated by non-living material, which is called an extracellular matrix. This matrix can be liquid or rigid, for example, blood contains plasma as its matrix and bones matrix is rigid. Connective tissue gives shape to organs and holds them in place, blood, bone, tendon, ligament, adipose and areolar tissues are examples of connective tissues. One method of classifying tissues is to divide them into three types, fibrous connective tissue, skeletal connective tissue, and fluid connective tissue. Muscle cells form the active contractile tissue of the known as muscle tissue or muscular tissue. Muscle tissue functions to force and cause motion, either locomotion or movement within internal organs. Cells comprising the nervous system and peripheral nervous system are classified as nervous tissue
10.
Estradiol (medication)
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Estradiol, also spelled oestradiol, is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in hormone replacement therapy for menopause, hypogonadism and it is also used in hormonal contraception and sometimes in the treatment of hormone-sensitive cancers like prostate cancer. Side effects of estradiol in women include breast tenderness and enlargement, headache, fluid retention, men and children who are exposed to estradiol may develop symptoms of feminization, such as breast development, and men may also experience hypogonadism and infertility. It may increase the risk of endometrial hyperplasia and endometrial cancer in women with an intact uterus if it is not taken together with a progestogen like progesterone, Estradiol should not be used in women who are pregnant or breastfeeding or who have breast cancer. Estradiol was first isolated in 1935 and it first became available as a medication, in the form of estradiol benzoate, a prodrug of estradiol, in 1936. Micronized estradiol, which allowed estradiol to be taken by mouth, was not introduced until 1975, Estradiol is also used as other prodrugs like estradiol valerate and estradiol acetate. Related estrogens such as ethinylestradiol, which is the most common estrogen in oral contraceptives, Estradiol is used in hormone replacement therapy to treat moderate to severe menopausal symptoms such as hot flashes, vaginal dryness and atrophy, and osteoporosis. Estradiol is used as part of hormone replacement therapy for transgender women, parenteral estradiol is largely free of the cardiovascular side effects of the high oral dosages of synthetic estrogens that were used previously. However, side effects such as gynecomastia and feminization in general may be difficult to tolerate or unacceptable for many men, estrogens are effective in the treatment of about 35% of cases of breast cancer and have comparable effectiveness to antiestrogens like the selective estrogen receptor modulator tamoxifen. Estrogens may be used in treatment of infertility in women when there is a need to develop sperm-friendly cervical mucous or an appropriate uterine lining, estrogens can be used to suppress and cease lactation and breast engorgement in postpartum women who do not wish to breastfeed. They do this by directly decreasing the sensitivity of the alveoli of the glands to the lactogenic hormone prolactin. Estrogens have been used to limit final height in adolescent girls with tall stature, Estradiol should not be taken by people with a hypersensitivity/allergy or those who are pregnant or are suspected pregnant. The most common effects of estradiol in women include breast tenderness, breast enlargement, headache, fluid retention. Cardiovascular, chest pain, deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke, cutaneous, chloasma or melasma, erythema multiforme, erythema nodosum, otitis media, hemorrhagic eruption, loss of scalp hair, pruritus, or rash. Ocular, retinal vascular thrombosis, steepening of corneal curvature or intolerance to contact lenses, central, headache, migraine, dizziness, chorea, nervousness/anxiety, mood disturbances, irritability, changes in libido, worsening of epilepsy, and increased risk of dementia. Estrogens should only be used for the shortest possible time and at the lowest effective dose due to these risks, attempts to gradually reduce the medication via a dose taper should be made every three to six months. Inducers of cytochrome P450 enzymes like CYP3A4 such as St. Estradiol is an estrogen, or an agonist of the estrogen receptors, ERα. It is also an agonist of the estrogen receptors such as the GPER, Gq-mER
11.
Valeric acid
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Valeric acid, or pentanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula C5H10O2. Like other low-molecular-weight carboxylic acids, it has an unpleasant odor. It is found naturally in the flowering plant valerian, from which it gets its name. Its primary use is in the synthesis of its esters, volatile esters of valeric acid tend to have pleasant odors and are used in perfumes and cosmetics. Ethyl valerate and pentyl valerate are used as food additives because of their fruity flavors and it differs from valproic acid simply by lacking a 3-carbon side-chain. Mevalonic acid is derived from valeric acid by methylation, valeric acid can cause irritation if it comes into contact with the skin, eyes, or mucous membranes. 4-Hydroxy-4-methylpentanoic acid Pivalic acid 3-Methylbutanoic acid, also called isovaleric acid
12.
Estradiol
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Estradiol, also spelled oestradiol, is a steroid, an estrogen, and the primary female sex hormone. It is named for and is important in the regulation of the estrous, while estrogen levels in men are lower compared to women, estrogens have essential functions in men as well. Estradiol is found in most vertebrates as well as crustaceans, insects, fish. Estradiol is produced especially within the follicles of the female ovaries, estradiol is biosynthesized from cholesterol through a series of chemical intermediates. One principal pathway involves the generation of 4-androstenedione, which is converted into estrone by aromatase, alternatively, 4-androstenedione can be converted into testosterone, an androgen and the primary male sex hormone, which in turn can be aromatized into estradiol. The development of sex characteristics in women is driven by estrogens, to be specific. These changes are initiated at the time of puberty, most are enhanced during the reproductive years, thus, estradiol produces breast development, and is responsible for changes in the body shape, affecting bones, joints, and fat deposition. Fat structure and skin composition are modified by estradiol and it enhances growth of the myometrium. Estradiol appears necessary to maintain oocytes in the ovary, in the luteal phase, estradiol, in conjunction with progesterone, prepares the endometrium for implantation. During pregnancy, estradiol increases due to placental production, the effect of estradiol, together with estrone and estriol, in pregnancy is less clear. They may promote blood flow, myometrial growth, stimulate breast growth and at term, promote cervical softening. In baboons, blocking of estrogen production leads to pregnancy loss, research is investigating the role of estrogens in the process of initiation of labor. Actions of estradiol are required before the exposure of progesterone in the luteal phase, the effect of estradiol upon male reproduction is complex. Estradiol is produced by action of aromatase mainly in the Leydig cells of the testis, but also by some germ cells. It functions to prevent apoptosis of male sperm cells, suppression of estradiol production in a subpopulation of subfertile men may improve the semen analysis. Males with certain sex chromosome genetic conditions, such as Klinefelters syndrome, estradiol has a profound effect on bone. Individuals without it will become tall and eunuchoid, as epiphyseal closure is delayed or may not take place, bone structure is affected also, resulting in early osteopenia and osteoporosis. Also, women past menopause experience a loss of bone mass due to a relative estrogen deficiency
13.
Pharmacodynamics
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Pharmacodynamics is the study of the biochemical and physiologic effects of drugs. The effects can include those manifested within animals, microorganisms, or combinations of organisms, Pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. Both together influence dosing, benefit, and adverse effects, Pharmacodynamics is sometimes abbreviated as PD and pharmacokinetics as PK, especially in combined reference. Pharmacodynamics places particular emphasis on relationships, that is, the relationships between drug concentration and effect. One dominant example is drug-receptor interactions as modeled by L + R ⇌ L ⋅ R where L, R, and LR represent ligand, receptor and this equation represents a simplified model of reaction dynamics that can be studied mathematically through tools such as free energy maps. Antacids and chelating agents combine chemically in the body, the widest class of drugs act as ligands which bind to receptors which determine cellular effects. Upon drug binding, receptors can elicit their normal action, blocked action, in principle, a pharmacologist would aim for a target plasma concentration of the drug for a desired level of response. In reality, there are factors affecting this goal. Pharmacokinetic factors determine peak concentrations, and concentrations cannot be maintained with absolute consistency because of metabolic breakdown, genetic factors may exist which would alter metabolism or drug action itself, and a patients immediate status may also affect indicated dosage. The duration of action of a drug is the length of time that particular drug is effective, the binding of ligands to receptors is governed by the law of mass action which relates the large-scale status to the rate of numerous molecular processes. The rates of formation and un-formation can be used to determine the concentration of bound receptors. The equilibrium dissociation constant is defined by, L + R ↔ L ⋅ R K d = where L=ligand, R=receptor, the fraction of bound receptors is known as occupancy. The relationship between occupancy and pharmacological response is usually non-linear and this explains the so-called receptor reserve phenomenon i. e. the concentration producing 50% occupancy is typically higher than the concentration producing 50% of maximum response. The simplest interpretation of receptor reserve is that it is a model that states there are excess receptors on the surface than what is necessary for full effect. Thus, the existence of receptor reserve depends on the agonist, tissue, as receptor reserve is very sensitive to agonist’s intrinsic efficacy, it is usually defined only for full agonists. Often the response is determined as a function of log to consider many orders of magnitude of concentration, however, there is no biological or physical theory which relates effects to the log of concentration. It is just convenient for graphing purposes and it is useful to note that 50% of the receptors are bound when =Kd. The graph shown represents the conc-response for two hypothetical receptor agonists, plotted in a semi-log fashion, the curve toward the left represents a higher potency since lower concentrations are needed for a given response
14.
Excretion
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Excretion is the process by which metabolic wastes and other non-useful materials are eliminated from an organism. In vertebrates this is carried out by the lungs, kidneys. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell, excretion is an essential process in all forms of life. For example, in urine is expelled through the urethra. In unicellular organisms, waste products are discharged directly through the surface of the cell, green plants produce carbon dioxide and water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis, oxygen is a by product generated during photosynthesis, and exits through stomata, root cell walls, and other routes. Plants can get rid of water by transpiration and guttation. These latter processes do not need added energy, they act passively, however, during the pre-abscission phase, the metabolic levels of a leaf are high. Plants also excrete some waste substances into the soil around them, in animals, the main excretory products are carbon dioxide, ammonia, urea, uric acid, guanine and creatine. The liver and kidneys clear many substances from the blood, aquatic animals usually excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution. In terrestrial animals ammonia-like compounds are converted into other materials as there is less water in the environment. Birds excrete their nitrogenous wastes as uric acid in the form of a paste and this is metabolically more expensive, but allows more efficient water retention and it can be stored more easily in the egg. Many avian species, especially seabirds, can also excrete salt via specialized nasal salt glands, in insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is actively transported into the tubule, which transports the wastes to the intestines, the metabolic waste is then released from the body along with fecal matter. The excreted material may be called dejecta or ejecta, in pathology the word ejecta is more commonly used. UAlberta. ca, Animation of excretion Brian J Ford on leaf fall in Nature
15.
Urine
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Urine is a liquid by-product of metabolism in the bodies of many animals, including humans. It is expelled from the kidneys and flows through the ureters to the urinary bladder, cellular metabolism generates numerous by-products, many nitrogenous, that require clearance from the bloodstream. These by-products are eventually expelled from the body during urination, the method for excreting water-soluble chemicals from the body. These chemicals can be detected and analyzed by urinalysis, of the many such substances that exist, the three main nitrogenous wastes of the mammalian body are urea, uric acid, and creatinine. Animal urine forms part of the nitrogen cycle, in balanced ecosystems it fertilizes soil and plants, which in turn continue to support the animal population. Some animals use it to mark their territories, human urine and human feces are collectively referred to as human waste, as sewage, they require sewage treatment in places where population density is high. Livestock urine and feces similarly require proper management if the population density is high. Such management is part of ecological sanitation, most animals have excretory systems for elimination of soluble toxic wastes. In humans, soluble wastes are excreted primarily by the system and, to a lesser extent in terms of urea. The urinary system consists of the kidneys, ureters, urinary bladder, the system produces urine by a process of filtration, reabsorption, and tubular secretion. The kidneys extract the soluble wastes from the bloodstream, as well as water, sugars. The resulting urine contains high concentrations of urea and other substances, urine flows from the kidney through the ureter, bladder, and finally the urethra before passing from the body. Research looking at the duration of urination in a range of species found that 9 larger species urinated for 21 ±13 seconds irrespective of body size. Smaller species including rodents and bats cannot produce jets and instead urinate with a series of drops, producing too much or too little urine needs medical attention. Polyuria is a condition of excessive production of urine, oliguria when <400 mL are produced, about 91-96% of urine consists of water. Urine also contains an assortment of inorganic salts and organic compounds, including proteins, hormones, the total solids in urine are on average 59 g per person per day. Organic matter makes up between 65% and 85% of urine dry solids, with volatile solids comprising 75–85% of total solids, urea is the largest constituent of the solids, constituting more than 50% of the total. On an elemental level, human urine contains 6.87 g/L carbon,8.12 g/L nitrogen,8.25 g/L oxygen, the exact proportions vary with individuals and with factors such as diet and health
16.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
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ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
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ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
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European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list
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Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
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Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
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Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
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International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
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Side effect
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Occasionally, drugs are prescribed or procedures performed specifically for their side effects, in that case, said side effect ceases to be a side effect, and is now an intended effect. For instance, X-rays were historically used as an imaging technique, buprenorphine has been shown experimentally to be effective against severe, refractory depression. Bupropion, an anti-depressant, is used as a smoking cessation aid, this indication was later approved. In Ontario, Canada, smoking cessation drugs are not covered by provincial drug plans, elsewhere, Zyban is priced higher than Wellbutrin, therefore, some physicians prescribe Wellbutrin for both indications. Dexamethasone and Betamethasone in premature labor, to enhance pulmonary maturation of the fetus, doxepin has been used to treat angiodema and severe allergic reactions due to its strong antihistamine properties. Hydroxyzine, an antihistamine, is used as an anxiolytic. Magnesium sulfate in obstetrics for premature labor and preeclampsia, methotrexate, approved for the treatment of choriocarcinoma, is frequently used for the medical treatment of an unruptured ectopic pregnancy. The SSRI medication sertraline is approved as an antidepressant but delays conjugal climax in men, sildenafil was originally intended for pulmonary hypertension, subsequently, it was discovered that it also produces erections, for which it was later marketed. Terazosin, an α1-adrenergic antagonist approved to treat benign prostatic hyperplasia, echinacea – more than 20 different types of reactions have been reported, including asthma attacks, loss of pregnancy, hives, swelling, aching muscles and gastrointestinal upsets. Feverfew – pregnant women should avoid using this herb, as it can trigger uterine contractions, in animal experiments, the use of feverfew was found to trigger spontaneous abortions. Asteraceae plants – which include feverfew, echinacea, dandelion and chamomile, side effects include allergic dermatitis and hay fever
. PMID 21151673.