A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, amino acids, other chemicals; these blockers act as ion channel antagonists, preventing the response, provided by the opening of the channel. Ion channels permit the selective passage of ions through cell membranes by utilizing proteins that function as pores, which allow for the passage of electrical charge in and out of the cell; these ion channels are most gated, meaning they require a specific stimulus to cause the channel to open and close. These ion channel types regulate the flow of charged ions across the membrane and therefore mediate membrane potential of the cell. Molecules that act as channel blockers are important in the field of pharmacology, as a large portion of drug design is the use of ion channel antagonists in regulating physiological response.
The specificity of channel block molecules on certain channels makes it a valuable tool in the treatment of numerous disorders. To comprehend the mechanism of channel blockers, it is critical to understand the composition of ion channels, their main function is to contribute to the resting membrane potential of a cell via the flow of ions through a cell membrane. To accomplish this task, ions must be able to cross the hydrophobic region of a lipid bilayer membrane, an unfavorable process. To assist in ion transport, ion channels form a hydrophilic pore through the membrane which allows for the unfavorable transfer of hydrophilic molecules. Various ion channels have varying mechanisms of function, they include: voltage-gated ion channels Ion channels that are activated by changes in membrane potential ligand-gated ion channel Ion channels mediated by the binding of small molecules to the channel protein mechanosensitive ion channels Ion channels that respond to stretch, vibration, or temperature changes light-gated ion channels Ion channels that open or close in response to lightMolecules that act as ion channel blockers can be used in relation to any of these various channels.
For example, sodium channels, which are essential to the production of action potentials, are affected by many different toxins. Tetrodotoxin, a toxin found in pufferfish blocks sodium ion transportation by blocking the selectivity filter region of the channel. Much of the structure of the pores of ion channels has been elucidated from studies that used toxins to inhibit channel function. Tools such as X-ray crystallography and electrophysiology have been essential in locating the binding sites of open channel block molecules. By studying the biological and chemical makeup of ion channels, researchers can determine the makeup of the molecules that bind to certain regions. X-ray crystallography provides a structural image of the molecule in question. Determining the hydrophobicity of channel domains through hydrophobicity plots provides clues to the chemical makeup of the molecule and why it binds to a certain region. For example, if a protein binds to a hydrophobic region of the channel, the molecule in question might be composed of the amino acids alanine, leucine, or phenylalanine, as they are all hydrophobic themselves.
Electrophysiology is an important tool in identifying channel structure, as analyzing the ionic factors that lead to channel activation can be critical to understanding the inhibiting actions of open channel block molecules. Channel blockers are antagonists for the channels required to produce normal physiological function in cells. Many channels have binding spots for regulatory elements which can promote or repress normal function depending on the requirements within the cell and organism; the normal function of agonist binding is the generation of cellular changes leading to various downstream effects. Conversely, when open channel blockers bind to the cell they prevent the normal function of agonist binding. For example, voltage-gated channels open and close based on membrane potential and are critical in the generation of action potentials by their allowance of ions to flow down established gradients. However, open channels blockers can bind to these channels to prevent ions from flowing, thus inhibiting the initiation of an action potential.
Many different organic compounds can act as channel blockers despite channel specificity. Channels have evolved structures that, due to their membrane spanning regions, can discriminate between various ions or compounds. For example, some objects are too large for to fit into channels that are structurally specified to transport smaller objects, such as a potassium ion attempting to fit into a sodium channel. Conversely, some objects are too small to be properly stabilized by certain channel pores, such as a sodium ion attempting to pass through a potassium channel. In both cases, channel flux is not permitted. However, as long as a particular compound possesses adequate chemical affinity to a channel, that compound may be able to bind and block the channel pore. For example, TTX can bind and inactivate voltage-gated sodium channels, despite the fact that TTX is much larger and chemically different than sodium ions. Given the disparities in size and chemical properties between TTX and a sodium ion, this is an example of structure being used to block specific channels.
A channel block can be induced by many different types of organic compounds as long as they can bind to some portion of the target channel's pore. The kinetics of channel blockers are understood though their use as anesthetics. Local anesthet
Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or delay premature labor, among other things; these drugs can act through several mechanisms, such as directly activating postsynaptic receptors, blocking breakdown and reuptake of certain neurotransmitters, or stimulating production and release of catecholamines. The mechanisms of sympathomimetic drugs can be direct-acting, such as α-adrenergic agonists, β-adrenergic agonists, dopaminergic agonists. For maximum sympathomimetic activity, a drug must have: Amine group two carbons away from an aromatic group A hydroxyl group at the chiral beta position in the R-configuration Hydroxyl groups in the meta and para position of the aromatic ring to form a catechol, essential for receptor bindingThe structure can be modified to alter binding.
If the amine is primary or secondary, it will have direct action, but if the amine is tertiary, it will have poor direct action. If the amine has bulky substituents it will have greater beta adrenergic receptor activity, but if the substituent is not bulky it will favor the alpha adrenergic receptors. Direct stimulation of the α- and β-adrenergic receptors can produce sympathomimetic effects. Salbutamol is a used direct-acting β2-agonist. Other examples include phenylephrine and dobutamine. Stimulation of the D1 receptor by dopaminergic agonists such as fenoldopam is used intravenously to treat hypertensive crisis. Dopaminergic stimulants such as amphetamine and propylhexedrine work by causing the release of dopamine and norepinephrine, along with blocking the reuptake of these neurotransmitters. A primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity; the pKa of the amine is 8.5-10. The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha- and beta-adrenergic activity.
Substances such as cocaine affect dopamine, some substances such as MDMA affect serotonin. Norepinephrine is synthesized by the body from the amino acid tyrosine, is used in the synthesis of epinephrine, a stimulating neurotransmitter of the central nervous system. Thus, all sympathomimetic amines fall into the larger group of stimulants. In addition to intended therapeutic use, many of these stimulants have abuse potential, can induce tolerance, physical dependence, although not by the same mechanism as opioids or sedatives; the symptoms of physical withdrawal from stimulants can include fatigue, dysphoric mood, increased appetite, vivid or lucid dreams, hypersomnia or insomnia, increased movement or decreased movement and drug craving, as is apparent in the rebound withdrawal from certain substituted amphetamines. Physical withdrawal from some sedatives can be lethal, for instance benzodiazepine withdrawal syndrome. Opioid withdrawal is uncomfortable described as a bad case of the flu, with severe abdominal cramps and diarrhoea as central symptoms, but it is lethal unless the user has a comorbid condition.
"Parasympatholytic" and "sympathomimetic" have similar effects, but through different pathways. For example, both cause mydriasis, but parasympatholytics reduce accommodation while sympathomimetics do not. Amphetamine benzylpiperazine cathine cathinone cocaine ephedrine lisdexamfetamine maprotiline MDMA methamphetamine methcathinone methylenedioxypyrovalerone methylphenidate 4-methylaminorex oxymetazoline pemoline phenmetrazine propylhexedrine pseudoephedrine Sympathetic nervous system Sympatholytic Amines,+Sympathomimetic at the US National Library of Medicine Medical Subject Headings
H2 antagonists, sometimes referred to as H2RA and called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. This decreases the production of stomach acid. H2 antagonists can be used in the treatment of dyspepsia, peptic ulcers and gastroesophageal reflux disease, they have been surpassed by proton pump inhibitors. H2 antagonists are a type of antihistamine, although in common use the term "antihistamine" is reserved for H1 antagonists, which relieve allergic reactions. Like the H1 antagonists, some H2 antagonists function as inverse agonists rather than receptor antagonists, due to the constitutive activity of these receptors; the prototypical H2 antagonist, called cimetidine, was developed by Sir James Black at Smith, Kline & French – now GlaxoSmithKline – in the mid-to-late 1960s. It was first marketed in 1976 and sold under the trade name Tagamet, which became the first blockbuster drug; the use of quantitative structure-activity relationships led to the development of other agents – starting with ranitidine, first sold as Zantac, which has fewer adverse effects and drug interactions and is more potent.
Cimetidine ranitidine famotidine nizatidine roxatidine lafutidine Cimetidine was the prototypical histamine H2-receptor antagonist from which drugs were developed. Cimetidine was the culmination of a project at Smith, Kline & French by James W. Black, C. Robin Ganellin, others to develop a histamine receptor antagonist that would suppress stomach acid secretion. In 1964, it was known that histamine stimulated the secretion of stomach acid, that traditional antihistamines had no effect on acid production. From these facts the SK&F scientists postulated the existence of two different types of histamine receptors, they designated the one acted upon by the traditional antihistamines as H1, the one acted upon by histamine to stimulate the secretion of stomach acid as H2. The SK&F team used a classical design process starting from the structure of histamine. Hundreds of modified compounds were synthesised in an effort to develop a model of the then-unknown H2 receptor; the first breakthrough was Nα-guanylhistamine, a partial H2-receptor antagonist.
From this lead, the receptor model was further refined, which led to the development of burimamide, a specific competitive antagonist at the H2 receptor. Burimamide is 100 times more potent than Nα-guanylhistamine, proving its efficacy on the H2 receptor; the potency of burimamide was still too low for oral administration. And efforts on further improvement of the structure, based on the structure modification in the stomach due to the acid dissociation constant of the compound, led to the development of metiamide. Metiamide was an effective agent, it was proposed that the toxicity arose from the thiourea group, similar guanidine analogues were investigated until the discovery of cimetidine, which would become the first clinically successful H2 antagonist. Ranitidine was developed by Glaxo, in an effort to match the success of Smith, Kline & French with cimetidine. Ranitidine was the result of a rational drug design process utilising the by-then-fairly-refined model of the histamine H2 receptor and quantitative structure-activity relationships.
Glaxo refined the model further by replacing the imidazole-ring of cimetidine with a furan-ring with a nitrogen-containing substituent, in doing so developed ranitidine. Ranitidine was found to have a far-improved tolerability profile, longer-lasting action, ten times the activity of cimetidine. Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988; the H2-receptor antagonists have since been superseded by the more effective proton pump inhibitors, with omeprazole becoming the biggest-selling drug for many years. The H2 antagonists are competitive antagonists of histamine at the parietal cell's H2 receptor, they suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: Histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors, which stimulate acid secretion. H2-antagonists are used by clinicians in the treatment of acid-related gastrointestinal conditions, including: Peptic ulcer disease Gastroesophageal reflux disease Dyspepsia Prevention of stress ulcer Prevention of aspiration pneumonitis during surgery.
Oral H2-antagonists reduce gastric acidity and volume and have shown to reduce the frequency of aspiration pneumonitis. People who suffer from infrequent heartburn may take either antacids or H2-receptor antagonists for treatment; the H2-antagonists offer several advantages over antacids, including longer duration of action, greater efficacy, ability to be used prophylactically before meals to reduce the chance of heartburn occurring. Proton pump inhibitors, are the preferred treatment for erosive esophagitis since they have been shown to promote healing better than H2-antagonists. H2 antagonists are, in general, well-tolerated, except for cimetidine
Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal or glial cell after it has performed its function of transmitting a neural impulse. Reuptake is necessary for normal synaptic physiology because it allows for the recycling of neurotransmitters and regulates the level of neurotransmitter present in the synapse, thereby controlling how long a signal resulting from neurotransmitter release lasts; because neurotransmitters are too large and hydrophilic to diffuse through the membrane, specific transport proteins are necessary for the reabsorption of neurotransmitters. Much research, both biochemical and structural, has been performed to obtain clues about the mechanism of reuptake; the first primary sequence of a reuptake protein was published in 1990. The technique for protein sequence determination relied upon the purification and cloning of the transporter protein in question, or expression cloning strategies in which transport function was used as an assay for cDNA species coding for that transporter.
After separation, it was realized. Further exploration in the field of reuptake proteins found that many of the transporters associated with important neurotransmitters within the body were very similar in sequence to the GABA and norepinephrine transporters; the members of this new family include transporters for dopamine, serotonin, proline and GABA. They were called Na+/Cl− dependent neurotransmitter transporters. Sodium and chloride ion dependence will be discussed in the mechanism of action. Using the commonalities among sequences and hydropathy plot analyses, it was predicted that there are 12 hydrophobic membrane spanning regions in the ‘Classical’ transporter family. In addition to this, the N- and C-termini exist in the intracellular space; these proteins all have an extended extracellular loop between the third and fourth transmembrane sequences. Site-directed chemical labeling experiments verified the predicted topological organization of the serotonin transporter. In addition to neurotransmitter transporters, many other proteins in both animals and prokaryotes were found with similar sequences, indicating a larger family of Neurotransmitter:Sodium Symporters.
One of these proteins, LeuT, from Aquifex aeolicus, was crystallized by Yamashita et al. with high resolution, revealing a molecule of leucine and two Na+ ions bound near the center of the protein. They found that the transmembrane helices 1 and 6 contained unwound segments in the middle of the membrane. Along with these two helices, TM helices 3 and 8 and the areas surrounding the unwound sections of 1 and 6 formed the substrate and sodium ion binding sites; the crystal structure revealed pseudo-symmetry in LeuT, in which the structure of TM helices 1-5 is reflected in the structure of helices 6-10. There is an extracellular cavity in the protein, into which protrudes a helical hairpin formed by extracellular loop EL4. In TM1, an aspartate distinguishes monoamine NSS transporters from amino acid transporters which contain a glycine at the same position. External and internal “gates” were assigned to pairs of negatively and positively charged residues in the extracellular cavity and near the cytoplasmic ends of TM helices 1 and 8.
The classic transporter proteins use transmembrane ion gradients and electrical potential to transport neurotransmitter across the membrane of the presynaptic neuron. Typical neurotransmitter sodium symport transporters, which are Na+ and Cl− ion dependent, take advantage of both Na+ and Cl− gradients, inwardly directed across the membrane; the ions flow down their concentration gradients, in many cases leading to transmembrane charge movement, enhanced by the membrane potential. These forces pull the neurotransmitter substrate into the cell against its own concentration gradient. At a molecular level, Na+ ions stabilize amino acid binding at the substrate site and hold the transporter in an outward-open conformation that allows substrate binding; the role of the Cl− ion in the symport mechanism has been proposed to be for stabilizing the charge of the symported Na+. After ion and substrate binding have taken place, some conformational change must occur. From the conformational differences between the structure of TMs 1-5 and that of TMs 6-10, from the identification of a substrate permeation pathway between the binding site of SERT and the cytoplasm, a mechanism for conformational change was proposed in which a four-helix bundle composed of TMs 1, 2, 6 and 7 changes its orientation within the rest of the protein.
A structure of LeuT in the inward-open conformation subsequently demonstrated that the major component of the conformational change represents movement of the bundle relative to the rest of the protein. The main objective of a reuptake inhibitor is to decrease the rate by which neurotransmitters are reabsorbed into the presynaptic neuron, increasing the concentration of neurotransmitter in the synapse; this increases neurotransmitter binding to pre- and postsynaptic neurotransmitter receptors. Depending on the neuronal system in question, a reuptake inhibitor can have drastic effects on cognition and behavior. Non-competitive inhibition of the bacterial homologue LeuT by tricyclic antidepressants resulted from binding of these inhibitors in the extracellular permeation pathway. However, the competitive nature of serotonin transport inhibition by antidepressants suggests that in neurotransmitter transporters, they bind in a site overlapping the substrate site. Horschitz et al. examined reuptake inhibitor selectivity among the rat serotonin reuptake protein expressed in human em
Enzymes are macromolecular biological catalysts. Enzymes accelerate chemical reactions; the molecules upon which enzymes may act are called substrates and the enzyme converts the substrates into different molecules known as products. All metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps; the study of enzymes is called enzymology and a new field of pseudoenzyme analysis has grown up, recognising that during evolution, some enzymes have lost the ability to carry out biological catalysis, reflected in their amino acid sequences and unusual'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins; the latter are called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction rate by lowering its activation energy; some enzymes can make their conversion of substrate to product occur many millions of times faster.
An extreme example is orotidine 5'-phosphate decarboxylase, which allows a reaction that would otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the equilibrium of a reaction. Enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules: inhibitors are molecules that decrease enzyme activity, activators are molecules that increase activity. Many therapeutic drugs and poisons are enzyme inhibitors. An enzyme's activity decreases markedly outside its optimal temperature and pH, many enzymes are denatured when exposed to excessive heat, losing their structure and catalytic properties; some enzymes are used commercially, in the synthesis of antibiotics. Some household products use enzymes to speed up chemical reactions: enzymes in biological washing powders break down protein, starch or fat stains on clothes, enzymes in meat tenderizer break down proteins into smaller molecules, making the meat easier to chew.
By the late 17th and early 18th centuries, the digestion of meat by stomach secretions and the conversion of starch to sugars by plant extracts and saliva were known but the mechanisms by which these occurred had not been identified. French chemist Anselme Payen was the first to discover an enzyme, diastase, in 1833. A few decades when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that this fermentation was caused by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms, he wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."In 1877, German physiologist Wilhelm Kühne first used the term enzyme, which comes from Greek ἔνζυμον, "leavened" or "in yeast", to describe this process. The word enzyme was used to refer to nonliving substances such as pepsin, the word ferment was used to refer to chemical activity produced by living organisms.
Eduard Buchner submitted his first paper on the study of yeast extracts in 1897. In a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts when there were no living yeast cells in the mixture, he named the enzyme that brought about the fermentation of sucrose "zymase". In 1907, he received the Nobel Prize in Chemistry for "his discovery of cell-free fermentation". Following Buchner's example, enzymes are named according to the reaction they carry out: the suffix -ase is combined with the name of the substrate or to the type of reaction; the biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others argued that proteins were carriers for the true enzymes and that proteins per se were incapable of catalysis. In 1926, James B. Sumner crystallized it; the conclusion that pure proteins can be enzymes was definitively demonstrated by John Howard Northrop and Wendell Meredith Stanley, who worked on the digestive enzymes pepsin and chymotrypsin.
These three scientists were awarded the 1946 Nobel Prize in Chemistry. The discovery that enzymes could be crystallized allowed their structures to be solved by x-ray crystallography; this was first done for lysozyme, an enzyme found in tears and egg whites that digests the coating of some bacteria. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail. An enzyme's name is derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase. Examples are alcohol dehydrogenase and DNA polymerase. Different enzymes that catalyze the same chemical reaction are called isozymes; the International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers. The first number broadly classifies the enzyme based on its mechanism; the top-level classification is: EC 1, Oxidoreductases: catalyze oxidation/reducti
Autonomic nervous system
The autonomic nervous system the vegetative nervous system, is a division of the peripheral nervous system that supplies smooth muscle and glands, thus influences the function of internal organs. The autonomic nervous system is a control system that acts unconsciously and regulates bodily functions such as the heart rate, respiratory rate, pupillary response and sexual arousal; this system is the primary mechanism in control of the fight-or-flight response. Within the brain, the autonomic nervous system is regulated by the hypothalamus. Autonomic functions include control of respiration, cardiac regulation, vasomotor activity, certain reflex actions such as coughing, sneezing and vomiting; those are subdivided into other areas and are linked to ANS subsystems and nervous systems external to the brain. The hypothalamus, just above the brain stem, acts as an integrator for autonomic functions, receiving ANS regulatory input from the limbic system to do so; the autonomic nervous system has three branches: the sympathetic nervous system, the parasympathetic nervous system and the enteric nervous system.
Some textbooks do not include the enteric nervous system as part of this system. The sympathetic nervous system is considered the "fight or flight" system, while the parasympathetic nervous system is considered the "rest and digest" or "feed and breed" system. In many cases, both of these systems have "opposite" actions where one system activates a physiological response and the other inhibits it. An older simplification of the sympathetic and parasympathetic nervous systems as "excitatory" and "inhibitory" was overturned due to the many exceptions found. A more modern characterization is that the sympathetic nervous system is a "quick response mobilizing system" and the parasympathetic is a "more activated dampening system", but this has exceptions, such as in sexual arousal and orgasm, wherein both play a role. There are excitatory synapses between neurons. A third subsystem of neurons that have been named non-noradrenergic, non-cholinergic transmitters have been described and found to be integral in autonomic function, in particular in the gut and the lungs.
Although the ANS is known as the visceral nervous system, the ANS is only connected with the motor side. Most autonomous functions are involuntary but they can work in conjunction with the somatic nervous system which provides voluntary control; the autonomic nervous system is divided into the sympathetic nervous system and parasympathetic nervous system. The sympathetic division emerges from the spinal cord in the thoracic and lumbar areas, terminating around L2-3; the parasympathetic division has craniosacral “outflow”, meaning that the neurons begin at the cranial nerves and sacral spinal cord. The autonomic nervous system is unique in; the preganglionic, or first, neuron will begin at the “outflow” and will synapse at the postganglionic, or second, neuron's cell body. The postganglionic neuron will synapse at the target organ; the sympathetic nervous system consists of cells with bodies in the lateral grey column from T1 to L2/3. These cell bodies are "GVE" are the preganglionic neurons. There are several locations upon which preganglionic neurons can synapse for their postganglionic neurons: Paravertebral ganglia of the sympathetic chain cervical ganglia thoracic ganglia and rostral lumbar ganglia caudal lumbar ganglia and sacral gangliaPrevertebral ganglia Chromaffin cells of the adrenal medulla These ganglia provide the postganglionic neurons from which innervation of target organs follows.
Examples of splanchnic nerves are: Cervical cardiac nerves & thoracic visceral nerves, which synapse in the sympathetic chain Thoracic splanchnic nerves, which synapse in the prevertebral ganglia Lumbar splanchnic nerves, which synapse in the prevertebral ganglia Sacral splanchnic nerves, which synapse in the inferior hypogastric plexusThese all contain afferent nerves as well, known as GVA neurons. The parasympathetic nervous system consists of cells with bodies in one of two locations: the brainstem or the sacral spinal cord; these are the preganglionic neurons, which synapse with postganglionic neurons in these locations: Parasympathetic ganglia of the head: Ciliary, Submandibular and Otic In or near the wall of an organ innervated by the Vagus or Sacral nerves These ganglia provide the postganglionic neurons from which innervations of target organs follows. Examples are: The postganglionic parasympathetic splanchnic nerves The vagus nerve, which passes through the thorax and abdominal regions innervating, among other organs, the heart, lungs and stomach The sensory arm is composed of primary visceral sensory neurons found in the peripheral nervous system, in cranial sensory ganglia: the geniculate and nodose ganglia, appen
In biology, poisons are substances that cause disturbances in organisms by chemical reaction or other activity on the molecular scale, when an organism absorbs a sufficient quantity. The fields of medicine and zoology distinguish a poison from a toxin, from a venom. Toxins are poisons produced by organisms in nature, venoms are toxins injected by a bite or sting; the difference between venom and other poisons is the delivery method. Industry and other sectors employ poisonous substances for reasons other than their toxicity. Most poisonous industrial compounds have associated material safety data sheets and are classed as hazardous substances. Hazardous substances are subject to extensive regulation on production and use in overlapping domains of occupational safety and health, public health, drinking water quality standards, air pollution and environmental protection. Due to the mechanics of molecular diffusion, many poisonous compounds diffuse into biological tissues, water, or soil on a molecular scale.
By the principle of entropy, chemical contamination is costly or infeasible to reverse, unless specific chelating agents or micro-filtration processes are available. Chelating agents are broader in scope than the acute target, therefore their ingestion necessitates careful medical or veterinarian supervision. Pesticides are one group of substances whose toxicity to various insects and other animals deemed to be pests is their prime purpose. Natural pesticides have been used for this purpose for thousands of years. Bioaccumulation of chemically-prepared agricultural insecticides is a matter of concern for the many species birds, which consume insects as a primary food source. Selective toxicity, controlled application, controlled biodegradation are major challenges in herbicide and pesticide development and in chemical engineering as all lifeforms on earth share an underlying biochemistry. A poison which enters the food chain—whether of industrial, agricultural, or natural origin—might not be toxic to the first organism that ingests the toxin, but can become further concentrated in predatory organisms further up the food chain carnivores and omnivores concerning fat soluble poisons which tend to become stored in biological tissue rather than excreted in urine or other water-based effluents.
Two common cases of acute natural poisoning are theobromine poisoning of dogs and cats, mushroom poisoning in humans. Dogs and cats are not natural herbivores, but a chemical defense developed by Theobroma cacao can be incidentally fatal nevertheless. Many omnivores, including humans consume edible fungi, thus many fungi have evolved to become decisively inedible, in this case as a direct defense. Apart from food, many poisons enter the body through the skin and lungs. Hydrofluoric acid is a notorious contact poison, in addition to its corrosive damage. Occurring sour gas is a notorious, fast-acting atmospheric poison. Plant-based contact irritants, such as that possessed by poison ivy or poison oak, are classed as allergens rather than poisons. Poison can enter the body through the teeth, faulty medical implants, or by injection. In 2013, 3.3 million cases of unintentional human poisonings occurred. This resulted in 98,000 deaths worldwide, down from 120,000 deaths in 1990. In modern society, cases of suspicious death elicit the attention of the Coroner's office and forensic investigators.
While arsenic is a occurring environmental poison, its artificial concentrate was once nicknamed inheritance powder. In Medieval Europe, it was common for monarchs to employ personal food tasters to thwart royal assassination, in the dawning age of the Apothecary. Of increasing concern since the isolation of natural radium by Marie and Pierre Curie in 1898—and the subsequent advent of nuclear physics and nuclear technologies—are radiological poisons; these are associated with ionizing radiation, a mode of toxicity quite distinct from chemically active poisons. In mammals, chemical poisons are passed from mother to offspring through the placenta during gestation, or through breast milk during nursing. In contrast, radiological damage can be passed from mother or father to offspring through genetic mutation, which—if not fatal in miscarriage or childhood, or a direct cause of infertility—can be passed along again to a subsequent generation. Atmospheric radon is a natural radiological poison of increasing impact since humans moved from hunter-gatherer lifestyles though cave dwelling to enclosed structures able to contain radon in dangerous concentrations.
The 2006 poisoning of Alexander Litvinenko was a novel use of radiological assassination meant to evade the normal investigation of chemical poisons. Poisons dispersed into the environment are known as pollution; these are of human origin, but pollution can include unwanted biological processes such as toxic red tide, or acute changes to the natural chemical environment attributed to invasive species, which are toxic or detrimental to the prior ecology (especially if the prior ecology was associated with human economic valu