Content

Drug discovery Historical background Drug targets Screening & design Chemical diversity of natural products

Natural product drug discovery Structural elucidation

Lifestyle drug Drug injection

Advantages Disadvantages

Procedure Safer injection Risks History Modifications

Origin and early use Inverse benefit law State of affairs Impact Prescription Drugs Short-Term Effects of Drugs Effects of Specific Substances of Abuse Drug Dependency Drug Withdrawal Treatment How drugs affect your mental health Impact of Drug Trade on Physical & Mental Health

Impact on the Individual Impact on the Society

Observations and Theories on the Impact of Drugs on Crime Theoretical Perspectives Review of the Concept of the ‘Community Leader’ and its Relation to the ‘Drug Lord’ Analysis Critical Thoughts Action Plans

Drug discovery

In the field of medicine, biotechnology, and pharmacology drug discovery is the process by which new candidate medication is discovered. Historically, drugs were discovered through identifying the active ingredient from traditional remedies or by Serendipity discovery. Later chemical libraries of synthetic small molecule, natural products or extracts were screened in intact cells or whole organisms to identify substances that have a desirable Therapeutic effect in a process known classical Pharmacology. Since sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins, it has become common practice to use high through put screening of large compounds libraries against isolated biological targets which are hypothesized to be disease modifying in a process known as reverse pharmacology Hits from these screens are then tested in cells and then in animals for efficacy.Modern drug discovery involves the identification of screening hits medicinal chemistry and optimization of those hits to increase the affinity, selectivity, efficacy/potency stability, and oral bioavailability. Once a compound that fulfills all of these requirements has been identified, it will begin the process of drug development prior to clinical trials. One or more of these steps may, but not necessarily, involve computer-aided drug design.Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, "expensive, difficult, and inefficient process" with low rate of new therapeutic discovery. In 2010, the research and development cost of each new molecular entity (NME) was approximately US$1.8 billion. Drug discovery is done by pharmaceutical companies, with research assistance from universities. The "final product" of drug discovery is a patent on the potential drug. The drug requires very expensive Phase I, II and III clinical trials, and most of them fail. Small companies have a critical role, often then selling the rights to larger companies that have the resources to run the clinical trials.Discovering drugs that may be a commercial success, public health success, involves a complex interaction between investors, industry, academia, patent laws, regulatory exclusivity, marketing and the need to balance secrecy with communication.

Historical background

The idea that the effect of a drug in the human body is mediated by specific interactions of the drug molecule with biological macromolecules, led scientists to the conclusion that individual chemicals are required for the biological activity of the drug. This made for the beginning of the modern era in pharmacology, as pure chemicals, instead of crude extracts, became the standard drugs. Historically substances, whether crude extracts or purified chemicals were screened for biological activity without knowledge of the biological target. Only after an active substance was identified was an effort made to identify the target. This approach is known as classical pharmacology, forward pharmacology, or phenotypic drug discovery.Later, small molecules were synthesized to specifically target a known physiological/pathological pathway, rather than adopt the mass screening of banks of stored compounds. This led to great success, such as the work of Gertrude Elion and George H. Hitchings on purine metabolism , the work of James Black on beta blockers and cimetidine, and the discovery of statins by Akira Endo. Another champion of the approach of developing chemical analogues of known active substances was Sir David Jack at Allen and Danbury’s, later Glaxo, who pioneered the first inhaled selective beta2-adrenergic agonist for asthma, the first inhaled steroid for asthma, ranitidine as a successor to cimetidine, and supported the development of the trip tans. Of all these innovators, perhaps the most notable was Gertrude Elion. Working mostly with a group of fewer than 50 people on purine

analogues, she contributed to the discovery of the first anti-viral; the first immunosuppressant (azathioprine) that allowed human organ transplantation; the first drug to induce remission of childhood leukemia; pivotal anti-cancer treatments; an anti-malarial; an anti-bacterial; and a treatment for gout.Cloning of human proteins made possible the screening of large libraries of compounds against specific targets thought to be linked to specific diseases. This approach is known as reverse pharmacology and is the most frequently used approach today.

Drug targets

The definition of "target" itself is something argued within the pharmaceutical industry. Generally, the "target" is the naturally existing cellular or molecular structure involved in the pathology of interest that the drug-in-development is meant to act on. However, the distinction between a "new" and "established" target can be made without a full understanding of just what a "target" is. This distinction is typically made by pharmaceutical companies engaged in discovery and development of therapeutics. In an estimate from 2011, 435 human genome products were identified as therapeutic drug targets of FDA-approved drugs. "Established targets" are those for which there is a good scientific understanding, supported by a lengthy publication history, of both how the target functions in normal physiology and how it is involved in human pathology. This does not imply that the mechanism of action of drugs that are thought to act through a particular established targets is fully understood. Rather, "established" relates directly to the amount of background information available on a target, in particular functional information. The more such information is available, the less investment is (generally) required to develop a therapeutic directed against the target. The process of gathering such functional information is called "target validation" in pharmaceutical industry parlance. Established targets also include those that the pharmaceutical industry has had experience mounting drug discovery campaigns against in the past; such a history provides information on the chemical feasibility of developing a small molecular therapeutic against the target and can provide licensing opportunities and freedom-to-operate indicators with respect to small-molecule therapeutic candidates.In general, "new targets" are all those targets that are not "established targets" but which have been or are the subject of drug discovery campaigns. These typically include newly discovered proteins, or proteins whose function has now become clear as a result of basic scientific research.The majority of targets currently selected for drug discovery efforts are proteins. Two classes predominate: G-protein-coupled receptors (or GPCRs) and protein kinases.

Screening and design

The process of finding a new drug against a chosen target for a particular disease usually involves high-throughput screening (HTS), wherein large libraries of chemicals are tested for their ability to modify the target. Another important function of HTS is to show how selective the compounds are for the chosen target. The ideal is to find a molecule which will interfere with only the chosen target, but not other, related targets. To this end, other screening runs will be made to see whether the "hits" against the chosen target will interfere with other related targets - this is the process of cross-screening. Cross-screening is important, because the more unrelated targets a compound hits, the more likely that off-target toxicity will occur with that compound once it reaches the clinic.It is very unlikely that a perfect drug candidate will emerge from these early screening runs. It is more often observed that several compounds are found to have some degree of activity, and if these compounds share common chemical features, one or more can then be developed. At this

point, medicinal chemists will attempt to use structure-activity relationships (SAR) to improve certain features of the lead compound: increase activity against the chosen targetReduce activity against unrelated target improve the drug likeness or ADME properties of the molecule.This process will require several iterative screening runs, during which, it is hoped, the properties of the new molecular entities will improve, and allow the favored compounds to go forward to in vitro and in vivo testing for activity in the disease model of choice.Amongst the Physic-chemical properties associated with drug absorption include ionization and solubility; permeability can be determined by PAMPA and Caco-2. PAMPA is attractive as an early screen due to the low consumption of drug and the low cost compared to tests such as Caco-2, gastrointestinal tract (GIT) and Blood–brain barrier (BBB) with which there is a high correlation.A range of parameters can be used to assess the quality of a compound, or a series of compounds, as proposed in the Lipinski's Rule of Five. Such parameters include calculated properties such as to estimate lipophilicity, molecular weight, polar surface area and measured properties, such as potency, in-vitro measurement of enzymatic clearance etc. Some descriptors such as ligand efficiency and lipophilic efficiency combine such parameters to assess drug likeness.While HTS is a commonly used method for novel drug discovery, it is not the only method. It is often possible to start from a molecule which already has some of the desired properties. Such a molecule might be extracted from a natural product or even be a drug on the market which could be improved upon (so-called "me too" drugs). Other methods, such as virtual high throughput screening, where screening is done using computer-generated models and attempting to "dock" virtual libraries to a target, are also often used.Another important method for drug discovery is drug design, whereby the biological and physical properties of the target are studied, and a prediction is made of the sorts of chemicals that might (e.g.) fit into an active site. One example is fragment-based lead discovery (FBLD). Novel pharmacophores can emerge very rapidly from these exercises. In general, computer-aided drug design is often but not always used to try to improve the potency and properties of new drug leads.Once a lead compound series has been established with sufficient target potency and selectivity and favorable drug-like properties, one or two compounds will then be proposed for drug development. The best of these is generally called the lead compound, while the other will be designated as the "backup".Nature as source of drugs may be useful as a source of novel chemical structures for modern techniques of development of antibacterial therapies.Despite the implied potential, only a fraction of Earth’s living species has been tested for bioactive Traditionally many drugs and other chemicals with biological activity have been discovered by studying allelopathy - chemicals that organisms create that affect the activity of other organisms in the fight for survival.

Chemical diversity of natural products

As above mentioned, combinatorial chemistry was a key technology enabling the efficient generation of large screening libraries for the needs of high-throughput screening. However, now, after two decades of combinatorial chemistry, it has been pointed out that despite the increased efficiency in chemical synthesis, no increase in lead or drug candidates have been reached. This has led to analysis of chemical characteristics of combinatorial chemistry products, compared to existing drugs or natural products. Thechemoinformatics concept chemical diversity, depicted as distribution of compounds in the chemical space based on their physicochemical characteristics, is often used to describe the difference between the combinatorial chemistry libraries and natural products. The synthetic, combinatorial library compounds seem to cover only a limited and quite uniform chemical space,

whereas existing drugs and particularly natural products, exhibit much greater chemical diversity, distributing more evenly to the chemical space. The most prominent differences between natural products and compounds in combinatorial chemistry library number of chiral centers structure rigidity and number of aromatic moieties. Other chemical differences between these two groups include the nature of heteroatoms as well as level of non-aromatic unsaturation. As both structure rigidity and chirality are both well-established factors in medicinal chemistry known to enhance compounds specificity and efficacy as a drug, it has been suggested that natural products compare favorable to today's combinatorial chemistry libraries as potential lead molecules.Natural product drug discoveryThe main approach involves Ethno botany, the study of the general use of plants in society, and ethno pharmacology, an area inside ethno botany, which is focused specifically on medicinal uses.Structural elucidation The elucidation of the chemical structure is critical to avoid the re-discovery of a chemical agent that is already known for its structure and chemical activity. Mass spectrometry, often used to determine structure, is a method in which individual compounds are identified based on their mass/charge ratio, after ionization. Chemical compounds exist in nature as mixtures, so the combination of liquid chromatography and mass spectrometry (LC-MS) is often used to separate the individual chemicals. Databases of mass spectra’s for known compounds are available. Nuclear magnetic resonance spectroscopy is another important technique for determining chemical structures of natural products. NMR yields information about individual hydrogen and carbon atoms in the structure, allowing detailed reconstruction of the molecule’s architecture.

Lifestyle drug

Lifestyle drug is an imprecise term commonly applied to medications which treat non–life-threatening and non-painful condition such as baldness, impotence, wrinkles, erectile dysfunction, or acne, which the speaker perceives as either not medical problems at all or as minor medical conditions relative to others. It is sometimes intended as a pejorative, bearing the implication that the scarce medical research resources allocated to develop such drugs were spent frivolously when they could have been better spent researching cures for more serious medical conditions. Proponents, however, point out that improving the patient's subjective quality of life has always been a primary concern of medicine, and argue that these drugs are doing just that. It finds broad use in both media and scholarly journals.

There is direct impact of lifestyle drugs on society, particularly in the developing world. Implications associated with labeling of indications and products sales of these lifestyle drugs may be varied. Drugs can, over time, switch from 'lifestyle' to 'mainstream' use. Though no precise widely accepted definition or criteria are associated with the term, there is much debate within the fields of pharmacology and bioethics around the propriety of developing such drugs, particularly after the commercial debut of Viagra.The German government's health insurance scheme has denied insurance coverage for some Lebensstildroge ("lifestyle drugs") which they deem spurious.Critics of pharmaceutical firms claim that pharmaceutical firms actively musicalize; that is, they invent novel disorders and diseases which were not recognized as such before their "cures" could be profitably marketed, in effect anthologizing what were widely regarded as normal conditions of human existence. The consequences are said to include generally greater worries about health, misallocation of limited medical research resources to comparatively minor conditions while many

serious diseases remain uncured, and needless health care expenditure. This medicalization of some element of human condition has significance, in principle, as a matter for political discourse or dialogue in civil society concerning values or morals. Social critics also question the propriety of devoting huge research budgets towards creating these drugs when far more dangerous diseases like cancer and AIDS remain uncured. It is sometimes claimed that lifestyle drugs amount to little more than medically sanctioned recreational drug use.

Drug injection

"Shoot up" redirects here. For shooting video game genre, see Shoot 'me up.This article is not about medical practice. For medical practices, see Intramuscular injection or Intravenous therapy.

Fragment of hypodermic needle stuck inside arm of IV drug user (x-ray)Drug injection is a method of introducing a drug into the body with a hollow needle and a syringe which is pierced through the skin into the body (usually intravenous, but also intramuscular or subcutaneous). It often applies to substance dependence and recreational. This act is often colloquially referred to as "slamming", "shooting [up]", "banging", "pinning", or "jacking-up", often depending on the specific drug subculture in which the term is used (i.e. heroin, cocaine, methamphetamine).Although there are various methods of taking drugs, injection is favored by some users as the full effects of the drug are experienced very quickly, typically in five to ten seconds. It also bypasses first-pass metabolism in the liver, resulting in a higher bioavailability for many drugs than oral ingestion would (so users get a stronger effect from the same amount of the drug). This shorter, more intense high can lead to a dependency, both physical and psychological, developing more quickly than with other methods of taking drugs. As of 2004 there were 13.2 million people worldwide who used injection drugs of which 22% are from developed countries.

Advantages

There are a variety of reasons why drugs would be injected rather than taken through other methods.Increased effect — injecting a drug intravenously means that more of the drug will reach the brain more quickly. This means that the drug will have a very strong and rapid onset. With some drugs this can produce sensations not found with other routes of administration known as a rush.More efficient usage — A smaller amount is enough as injection means that more of the drug will reach the brain than with other methods. This is because the body's defenses and detoxifying mechanisms (such as first-pass metabolism in the liver with oral use) are bypassed. Injection increases a drug's bioavailability. This means that it requires less drug (and less money) to achieve the same effect (ignoring the effects of tolerance).Bypasses the digestive system some people with sensitive stomachs find it very unpleasant to swallow drugs because of persistent cramps or nausea.Does not harm the lungs or mucous membranes — the mucous membranes can be permanently damaged by habitual insufflation (snorting), and the lungs can be damaged by smoking.

Disadvantages

In addition to general problems associated with any IV drug administration (see risks of IV therapy) there are some specific problems associated with the informal injection of drugs by non-professionals.Increased chance of infection - This is generally a twofold problem.Needle sharing transmits blood-borne diseases between userAbscessed infections of injection sites are caused by lack of hygiene and a lack of aseptic technique.Increased chance of overdose — Because IV injection delivers a dose of drug straight into the bloodstream it is harder to gauge how much to use (as opposed to smoking or snorting where the dose can be increased incrementally until the desired effect is achieved). In addition, because of the rapid onset, overdose can occur very quickly, requiring immediate action.Scarring of the peripheral veins - This arises from the use of blunt injecting equipment. This is particularly common with users who have been injecting while in jail and re-use disposable syringes sometimes hundreds of times. IV drug use for an extended period may result in collapsed veins. Though rotating sites and allowing time to heal before reuse may decrease drug use. IV drug users are among the most difficult patient populations to obtain blood-specimens from because of peripheral venous scarring. The darkening of the veins due to scarring and toxin buildup produce tracks along the length of the veins and are known as track marks.Arterial damage — Arterial pseudo aneurysms may form at injection sites, which can rupture, potentially resulting in hemorrhage, distal ischemia, and gangrene. Inadvertent intra-arterial injection can also result in endarteritis and thrombosis, with ultimately similar consequences. Increased chance of addiction — the heightened effect of administering drugs intravenously can make the chances of addiction more likely.Social stigma — in many societies there is a social stigma attached to IV drug use, in addition to the more general stigma around illegal drug use and addiction. People who are satisfied taking drugs by other routes may not inject. This may be because of its perceived prevalence in inner cities and with lower-income people.

Procedure

A clandestine kit containing materials to inject drugsThe drug, usually in a powder or crystal form (though not always), is dissolved in water, normally in a spoon, tin, bottle cap, the bottom of a soda can, or another metal container. Cylindrical metal containers - sometimes called 'cookers'- are provided by needle exchanges. Users draw the required amount of water into a syringe and squirt this over the drugs. The solution is then mixed and heated from below if necessary. Heating is used mainly with heroin, (though not always, depending on the type of heroin)] but is also often used with other drugs, especially crushed tablets. Cocaine Hal (powdered cocaine) dissolves quite easily without heat. Heroin prepared for the European market is insoluble in water and usually requires the addition of an acid such as citric acid or ascorbic acid (Vitamin C) powder to dissolve the drug. Due to the dangers from using lemon juice or vinegar to

acidify the solution, packets of citric acid and Vitamin C powder are available at needle exchanges in Europe. In the U.S., vinegar and lemon juice are used to shoot crack cocaine. The acids convert the water-insoluble cocaine base in crack to a cocaine salt (cocaine acetate or cocaine citrate here) which is water soluble (like cocaine hydrochloride). Once the drugs are dissolved, a small syringe, usually 0.5 or 1 cc, is used to draw the solution through a filter, usually cotton from a cigarette filter or cotton swab (cotton bud). 'Tuberculin' syringes and types of syringes used to inject insulin are commonly used. Commonly used syringes usually have a built-in 28 gauge (or thereabouts) needle typically 1/2 or 5/8 inches long. The preferred injection site is the crook of the elbow (i.e., the Median cubical vein), on the user's non-writing hand. Other users opt to use the Basilica vein; While it may be easier to "hit", caution must be exercised as two nerves run parallel to the vein increasing the chance of nerve damage, as well as the chance of an arterial "nick".

A sterile and safe legitimate injection kit obtained from a needle-exchange programHarm reduction is an approach to public health intended to be a progressive alternative to an approach requiring complete abstinence from drug use. While it does not condone the taking of illicit drugs, it does seek to reduce the harms arising from their use, both for the person taking illicit drugs and the wider community.A prominent method for addressing the issue of disease transmission among intravenous drug users are needle exchange programs, in which facilities are available to exchange used injection equipment for safe sterile equipment, often without a prescription or fee. Such establishments also tend to offer free condoms to promote safe sex and reduce disease transmission. The idea is to slow disease transmission and promote public health by reducing the practice of sharing used needles. In countries where harm reduction programs are limited or non-existent, it is quite common for an IV user to use a single needle repeatedly or share with other users. It is also quite uncommon for a sterilizing agent to be used.

Safer injection

A philosophy of harm reduction promotes information and resources for IV drug users. General guidelines on safer injecting of various substances intravenously are typically based on the following

steps:The area for drug preparation should be cleaned with warm soapy water or an alcohol swab to minimize the risk of bacterial infection. The equipment required involves new syringes and needles, alcoholic swabs, rinse eye drops as sterile water, filter , tourniquet and a clean spoon or Steric up. In order to minimize the chance of bacteria or viruses entering the bloodstream, people are advised to wash their hands with soap and warm water. However, as people do not always have access to hot water and soap when they are injecting, the philosophy of harm reduction seeks to find the most realistic and reliable option that drug users will take: a process that takes much time or access to materiel is unlikely to be used frequently. Alcohol swabs are commonly distributed with injecting equipment, and while they are less effective than hand washing, their use is more effective than nothing. Any sharing of injecting

equipment, even tourniquets, is highly discouraged, due to the high danger of transmitting bacteria and viruses via the equipment.Sterile water is also recommended to prevent infection. Many needle and syringe programs distribute vials or ampoules of USP sterile water for this reason. Where sterile water is not obtainable, the harm reduction approach recommends tap water boiled for five minutes, and then allowed to cool.[5]

Once the water and substance are combined in the mixing vessel, heat is sometimes applied to assist the mixing. Filtering is recommended by health services, as the mix can consist of wax or other non-soluble materials which are damaging to veins. Additionally, the injection of talc has been associated with pulmonary talkies in intravenous drug users. Wheel filters are the most effective filters. 5.0 micron wheel filter (e.g. Apothecium Sterifilt), now shared in some needle-exchange programmers instead of cotton, is intended to get rid of the talc from prescription tablets like benzodiazepines, methadone tablets, and other recreational drugs like MDMA. However cotton wool (with the risk of cotton fever) or tampons can be used, although to be more effective, several filtrations should be performed; cigarette filters should not be used due to the risk of fibers breaking off and being injected along with the solution, nor should filters of any sort ever be re-used, either as filters or in an attempt to recover drug material present, due to many risks, ranging from cotton fever to life-threatening sepsis. Once the mix is drawn into the syringe, air bubbles should be removed by flicking the barrel with the needle pointed upwards and pressing the plunger to expel the bubbles that pool at the top. This is done to prevent injection of air into the bloodstream. The potential danger of an air embolism is often greatly overestimated by IV users; up to three CCs of air can be injected intravenously without causing complications, and time spent meticulously getting every minute air bubble out of the syringe would often be better spent ensuring clean conditions in general.A tourniquet can be used to assist vein access. The tourniquet should not be on too tight, or left on for too long, as this causes the veins to swell and stretch. When injecting, the needle's bevel or 'hole' should face upward and be eased into the vein at a shallow angle between 10 and 35 degrees to minimize the risk of penetrating through the vein entirely. In order to prevent stress on the vein, the needle should be pointing towards the heart. The plunger should be pulled back slightly (colloquially known as 'jacking back' or 'flagging') to ensure the needle is in the vein. Blood should appear in the barrel of the syringe if this is the case. This process is termed aspirating the needle or registering. When accessing a vein with unobstructed blood flow a "flashback," or sudden flash of red blood inside the needle tip, may occur spontaneously when the needle enters the vein. Because sudden appearance of blood in the needle/syringe alone does not guarantee proper needle placement (flashbacks can also occur when a needle passes through a vein completely, enters an artery inadvertently, or otherwise is extravagated), aspirating the plunger on the syringe is still considered a requisite step. The tourniquet should then be taken off and the plunger gently pushed. After injection, a clean tissue or cotton wool should be pressed against the injection site to prevent bleeding. Although many people use an alcohol swab for this purpose it is discouraged by health services as the alcohol interferes with blood clotting. Dispose of injecting gear using a 'sharps bin' if supplied. Other rigid-walled containers such as a bottle are recommended as a second best option.

Risks

An estimated 16 million people worldwide use intravenous drug, and approximately 3 million of these are believed to be HIV positive. The main symptoms for any blood-borne infections will usually appear a few days after infection has occurred and usually consists of a blocked and/or runny nose,

loss of taste, smell, other senses and an unpleasant sense of thickness in the forehead. A general feeling of malaise, aching and weakness will usually accompany these symptoms. If the onset of symptoms happens around 4–8 days after infection then it is more than likely hepatitis but could also be any strain of HIV. Sufferers tend to get these same symptoms regardless of what disease or virus they may have contracted.The most common symptoms of HIV or AIDS that has been contracted intravenously are again a runny and/or blocked nose, acute loss of taste and/or smell, a blocked or thick sensation within the head, general aching, malaise and weakness, hot and cold sweats and occasionally acute insomnia. These symptoms will most likely subside after 2–3 days and the individual will then regain their previous posture and well being. Any one individual could possibly live completely unaware of the presence of the virus for many years as the initial symptoms subside and may not appear again for a long time. Of all the ways to ingest drugs, injection, by far, carries the most risks as it bypasses the body's natural filtering mechanisms against viruses, bacteria and foreign objects. There will always be much less risk of overdose, disease, infections and health problems with alternatives to injecting, such as smoking, insufflation (snorting or nasal ingestion), or swallowing.Viruses such as HIV and hepatitis C are prevalent among IV drug users in many countries, mostly due to small groups sharing injection equipment combined with a lack of proper sterilization. Other health problems arise from poor hygiene and injection technique (be it IV, IM, or SC), such as cotton fever, phlebitis, abscesses, vein

collapse, ulcers, malaria,gas, tetanus, septicemia, thrombosis, embolism and all results thereof. Drug injection is also commonly a component in HIV-related syndics. Fragments from injection of pills are known to clog the small blood vessels of the lungs, brain and elsewhere, potentially causing pulmonary embolism, stroke, or venous embolism. A small proportion of pulmonary embolism (PE) is due to the embolization of air, fat, talc in drugs of intravenous drug abusers. More commonly, the inflammatory response to these foreign objects causes granulation tissue to form in the capillary beds, resulting in vacuities, and when it occurs in the pulmonary capillary bed, potentially pulmonary talkies. Hitting arteries and nerves is dangerous, painful, and presents its own similar spectrum of problems.

Modifications

Particularly for intravenous administration, self-injection in the arm can be awkward, and some people modify a syringe for single-handed operation by removing the plunger and affixing a bulb such as from a large dropper or baby pacifier to the end of the barrel to in effect make it a large dropper with a needle affixed. This is therefore a variant of the common method of injection with a dropper with the hypodermic needle affixed, using a "collar" made of paper or other material to create a seal between the needle and dropper. Removing part of the plunger assembly by cutting off most of the shaft and thumb rest and affixing the bulb to the end of the barrel, thereby allowing the bulb to operate the plunger by suction, also does work in many cases.An alternative to syringes in the 1970s was to use a glass medicine dropper, supposedly easier to manipulate with one hand. A large hairpin was used to make a hole in the skin and the dropper containing the drug (usually heroin) was inserted and the bulb squeezed, releasing it into the tissues. This method was also reported, by William S Burroughs and other sources, for intravenous administration at least as far back as 1930.

History

IV drug use is a relatively recent phenomenon arising from the invention of re-usable syringes and the synthesis of chemically pure morphine and cocaine.

It was noted that administering drugs intravenously strengthened their effect and since such drugs as heroin and cocaine were already being used to treat a wide variety of ailments, many patients were given injections of "hard" drugs for such ailments as alcoholism and depression.By the time of Leister Crowley intravenous drug culture already had a small, but loyal following. Sir Arthur Conan Doyle writes that Sherlock Holmes used to inject cocaine to occupy his mind between cases.Origin and early useThe hypodermic needle & syringe in its current form was invented by the French scientist Pravda in 1851 and became especially known during the wars of that and the subsequent decade, although the first well-known attempt to inject drugs into the body was a 1667 attempt to inject a solution of opium into a dog, and some had suspected that parenteral administration of drugs may work better based on the practice of rubbing opium and other drugs into sores or cuts on the skin for the purpose of causing systemic absorption and the beginnings of scientific understanding of the functioning of the lungs.During most of the 1850s, the previously-held belief that opiate dependence and addiction, often called "the opium appetite," (or when relevant the "morphine appetite" or "codeine appetite") was due to the drug's action on the digestive system—just like any hunger or thirst—caused doctors to opt to inject morphine rather than administer it orally in the hope that addiction would not develop; certainly by c.a. 1870 or earlier it was manifest that this was not the case and the title of earliest morphine addict as the term is currently understood is often given to Dry Pravda' wife although habituation through orally ingesting the drug was known before this time, including Returner and associates, followers, and his wife and dog. To some extent, it was also believed early on that bypassing the lungs would prevent opium addiction as well as habituation to tobacco. Ethanol in its usual form generally is not injected and can be very damaging by most routes of injection; in modern times it is used as an alternative or potentiate of phenol (carbolic acid) in procedures to ablate damaged nerves.In or shortly after 1851 the drugs which had been discovered and extracted from their plants of origin and refined into pure crystalline salts soluble in water included morphine(1804 or late 1803), codeine (1832), narcotine/noscapine (1803-1805?), papaverine (1814), cocaine (1855), caffeine (1819), quinine (1820), atropine (1831), scopolamine aka oscine aka laevo-duboisine (1833?), hyoscyamine or leave-atropine (1831), opium salts mixtures (c.a. 1840s) chloral derivatives (1831 et seq.), ephedrine (1836?), nicotine(1828) and many others of all types, psychoactive and not. Morphine in particular was used much more widely after the invention of the hypodermic syringe, and the practice of local anesthesia by infiltration was another step forward in medicine resulting from the hypodermic needle, discovered at around the same time that it was determined that cocaine produced useful numbing of the mucous membranes and eye.A wide variety of drugs are injected, among the most popular in many countries are morphine, heroin, cocaine, amphetamine and methamphetamine. Prescription drugs, including tablets, capsules, or even liquids or suppositories, are also occasionally injected, especially prescription opioids, since some opioid addicts already inject heroin. Injecting preparations not intended for this purpose is particularly dangerous because of the presence of excipients (fillers), which can cause blood clots. Injecting codeine into the bloodstream directly is dangerous because it causes a rapid histamine release, which can lead to potentially fatal anaphylaxis and pulmonary edema. Dihydrocodeine, hydrocodone, nicocodeine, and other codeine-based products carry similar risks. Codeine may instead be injected by the intramuscular or subcutaneous route. The effect will not be instant but the dangerous and unpleasant massive histamine release from the intravenous injection of codeine is avoided. To minimize the amount of dissolved material

in fluids prepared for injection, a filter of cotton or synthetic fiber is typically used, such as a cotton-swab tip or a small piece of cigarette filter.Some manufacturers add the narcotic antagonist naloxone or the anticholinergic atropine and homatropine (in lower than therapeutic doses) to their pills to prevent injection. Unlike naloxone, atropine does indeed help morphine and other narcotics combat neuralgia. The atropine may very well not present a problem, and there is the possibility of atropine content reduction of soluble tablets by placing them on an ink blotter with a drop of water on top, then preparing a shot from the remainder of the pill. Canada and many other countries prohibit manufacturers from including secondary active ingredients for the above reason; their Tailwind PX does not contain naloxone. However, as a narcotic agonist, pentazocine and its relatives can cause withdrawal in those physically dependent upon narcotics.

Inverse benefit law

The Inverse Benefit Law states that the ratio of benefits to harm among patients taking new drugs tends to vary inversely with how extensively a drug is marketed. Two Americans, Howard Brody and Donald Light, have defined the Inverse Benefit Law, inspired by Tudor Hart's Inverse care law.A drug effective for a serious disorder is less and less effective as it is promoted for milder cases and for other conditions for which the drug was not approved. As effectiveness becomes more diluted, the risks of harmful side effects proliferate, thus the benefit-harm ratio worsens as a drug is marketed more widely. The inverse benefit law highlights the need for comparative effectiveness research and other reforms to improve evidence-based prescribing. 

State of affairs

The law is manifested through 6 basic marketing strategies:Reducing thresholds for diagnosing disease,Relying on surrogate endpoints,Exaggerating safety claims,Exaggerating efficacy claims,Creating new diseases,Encouraging unapproved uses.

Impact

Much harm of new drugs is unexpected, and could be as serious as death. This is the reason why organizations like "Worst Pill, Best Pill" recommend not use/prescribe new medications before being in the market for at least ten years (except in the case of important new drugs that treat previously unsolved problems).Agencies of drugs, committee of ethics and organizations of patients' safety should consider:Requiring that clinical trials run long enough to pick up evidence of side effects and record all adverse reactions, including in subjects who drop out. Paying companies more for new drugs in proportion to how much better they are for patients than existing drugs, and marketing according to the value of the new drugs (ratio of benefits to harms and marketing). Considering that market could be a force against the best use of medications.

Prescription Drugs

AdderallAlprazolamAmbienAtivanClonazepam

HydrocodoneKlonopinClonazepamMethadoneOpiate

OxycodoneOxyContinPainkillerPercocetSuboxone

SubtextTramadolValiumViolinXanax

Short-Term Effects of Drugs

Different drugs can affect your sleep pattern. For example, stimulants cause you to stay awake much longer than normal, but when you come down from your high, you can be extremely fatigued. Depressants cause you to feel drowsy, so you might sleep more than normal when you take them. Opioids and hallucinogenic drugs also affect your sleep pattern, but the reaction you have to the drug determines whether you sleep more or less. Other common short-term side effects of drug use include memory loss, nausea and constipation.

Effects of Specific Substances of Abuse

Each drug affects your body in different ways. In addition, the long-term effects of drugs are different than the short-term effects.

Stimulants-like cocaine, crystal meth and amphetamines-give you an increased amount of energy. Repeated use of stimulants can cause violent behavior, panic attacks, psychosis and mood swings. People who abuse stimulants also have an increased risk of heart attack or stroke.Opioids, like heroin, Violin, Percocet and OxyContin, depress your respiration, so people who use opioids could develop pulmonary issues, such as pneumonia. They also have a risk of developing collapsed veins, liver disease and infections in the heart and valves.Depressants, like Ativan, Xanax and Klonopin, slow brain function, which often causes people to lose concentration easily and become dizzy and fatigued. Long-term effects of depressants use include sexual problems, sleep problems, breathing difficulties, chronic fatigue and depression. These drugs also increase your risk of developing high blood sugar and diabetes.Hallucinogenic can have psychological and physical effects on your body. Users can become paranoid, have mood swings, have outbursts of violence or develop extreme depression.If you’re battling a drug addiction and want to learn more about the effects of specific drugs, call (800) 943-0566.

Drug Dependency

Some people start using drugs simply to see what the drug high is like. Unfortunately, this begins the drug cycle, which eventually leads to a chemical dependency to the drug. People continue to use drugs because they don’t like the way their body feels when they come down from their high. The vicious cycle continues until their body develops a tolerance to drug, which causes them to consume it in higher does. Over time, a chemical dependency develops and their body doesn’t function correctly without the drug. According to the National Institute on Drug Abuse, addiction occurs when a chemical dependency to a drug is combined with an overwhelming urge to use the substance.

Drug Withdrawal Treatment

The first step to recovery is ridding your body of the substance. When you admit yourself to a detox clinic, you stay at the clinic while the drug leaves your system. Unfortunately, some people experience withdrawal symptoms during this time, but clinics have medical staff on hand to help you cope with your symptoms. The medical staff is allowed to administer medication, as needed, to help relieve any withdrawal symptoms you’re having. If you suffer from a drug addiction and need help finding a detox center in your area, call (800) 943-0566.

How drugs affect your mental health

Mental health means different things to different people. You may think of control, happiness, contentment, order – but good mental health is usually a sign of a positive way of life. Mental ill health is the opposite of this – it causes problems and creates barriers to being happy. Your frame of mind may vary between the two as mental health can change. It can be affected by external influences, and one of these is drugs.Drugs that are psychoactive, such as cannabis, alcohol, ecstasy and heroin, have the ability to affect your mood. They can arouse certain emotions or dampen down others. This may be why you use them. The changes in your mood or behavior caused by drugs are the result of changes to your brain. This is also the part of you that controls your mental health.Drugs interfere with the chemicals in your brain. This affects the messages those chemicals are trying to send. You need to weigh up both the short-term and long-term effects that drugs can have on your mental health.The short-term effects may well be something you enjoy – but probably only if they happen like you expect them to. You may also have unwanted short-term drug-induced side effects, such as acting or feeling strange. These are short-term because they pass as the drug leaves your system.Drugs can have a longer-lasting impact on your mental health too, and you need to think seriously about your own strengths and vulnerabilities. Consider whether you use drugs to make bad feelings go away and whether you are in control of your use. Even if you start using drugs with a clear mind they may still affect your mental health. Drugs can simply expose bad feelings you never knew you had.Unwanted effects may stay with you because you have a pre-existing mental health condition you were not aware of. Or you may get the dose very wrong and permanently disrupt a chemical balance in your brain.Short-term effects of drugs on mental healthAll psychoactive drugs may cause mental health problems while you are taking them and as you clear the drug from your body. These can include anxiety, mood swings, depression, sleep problems and psychosis.Drug-induced anxiety disorderYou may have panic attacks – periods of very severe anxiety when your heart rate increases, with trembling, sweats, shortness of breath, and a fear of losing control. You may also feel like your surroundings are strange and unreal, or that you are losing your personal identity and sense of reality.Drug-induced psychosisPsychoactive drugs can cause delusions – you believe things that aren’t true, or hallucinations – you see or hear things that are not there.Drug-induced mood disorderYou may have times when you feel depressed – sad, restless, irritable, tired, loss of pleasure, or manic – elevated mood, delusions, impulsive behavior, racing thoughts. This is called mood disorder and may be caused by drugs such as cocaine, amphetamines, heroin and methadone, to name a few.Long-term effects of drugs on mental healthPsychoactive drugs may cause you ongoing mental health problems. It is not clear why this happens to some people and not others. It may be that using a drug has triggered a mental illness you didn’t know you had, or the drug changes the way a certain chemical affects your brain functions. Here are some of the ways that different drugs can affect your mental health:

Ecstasy and depressionEcstasy is an amphetamine that causes hallucinations. It works by making serotonin more available and gives you a sense of euphoria when you take it. Serotonin is a chemical naturally found in your brain which regulates your mood. It is sometimes called the ‘happy hormone’. Ecstasy causes your brain to release a much higher amount of serotonin than usual. Over time your natural stores of serotonin may drop so much that you may never have the same levels as you had before you started using drugs. If lots of serotonin means euphoria than lack of serotonin means depression. You may experience short-term depression in the days after you use ecstasy but we need more research about the long term effects.Living with a dual diagnosisA dual diagnosis is when you have two separate conditions – a mental health problem and a drug addiction. The means that health services need to work together to best provide care.When trying to deal with both an addiction and a mental health disorder it is hard to know where one ends and the other begins. It may not be clear which came first. People with mental health problems sometimes use drugs to cope with the chaos, the bad emotions and the stigma of conditions such as depression or schizophrenia. But turning to drugs to cope with mental health problems can lead to complications of the illness and interfere with prescribed medication you are taking.The mental health problems that most often occur with drug misuse are depression, schizophrenia, bipolar disorder, anxiety disorder and attention-deficit hyperactivity disorder (ADHD).

Impact of Drug Trade on Physical & Mental HealthThe impact of the drug trade/abuse on the physical and mental health of the population can be categorized in terms of impact on the individual and on the society at large.

Impact on the Individual • Physical Health- Physical symptoms related to abuse – states off dependency, abuse, psychosis, poisoning or overdose.- Indirect effects of drug use – cirrhosis, nutritional or metabolic disorders, viral infections such as HIV/AIDS or hepatitis, trauma resulting from traffic accidents, other accidents or personal attacks.- Requirements for medical attention/hospitalization – loss of earnings, depletion of savings, poverty.- The ultimate price – death. • Mental Health Drug abuse can result in a number of disorders including: - Schizophrenia- Manic depression- Paranoia- Personality disorder- Depression- Anxiety- Panic attacks

- Agitation- Lower self -esteem

Impact on the Society The cumulative impact of individuals represents impact on the society. In this regard the costs are very virtually incalculable. It is the society that ultimately bears the costs associated with individual abuse including: - Treatment in public and private institutions, including hospital/rehab admissions and duration of stay.- Deaths or serious injuries by homicide, accident, or suicide associated with psychoactive substance use.- Increased stress and psychological burdens on society, especially in response to escalating serious crime rates associated with the trade including property loss, murders and kidnappings.- Cost of premature death.- Substance abuse reduction costs associated with creating awareness and encouraging attitudinal and behavior change for current, past and non-users.

Review of Responses to the Measures Applied to Combat the Drug Trade with special reference to International Conventions and Multilateral Plans of Action.Trinidad and Tobago has ratified an umber of international conventions and multi-lateral plans of action. It has also engaged in regional initiatives and bi-lateral arrangements with the United States, United Kingdom, Canada, Venezuela, Cuba and St. Kitts/Nevis.

Observations and Theories on the Impact of Drugs on Crime Definition of Crime:An act or commission of an act that is forbidden or the omission of a duty that is commanded by a public law and that makes the offender liable to punishment by that law; grave offence, especially against morality.

User Crimes - Pharmacologically-induced crimes – as people become ‘ mad’.- Economically-motivated crimes – acquisition-type crime to fund crack purchase.- Systemic crime – among rival groups of turf³.

Non-user (Distribution) Crimes - Laundering of illicit profits.- Intimidation/Elimination of witnesses.- Murders and kidnappings of competitors, colleagues, law enforcement, public/private officials.- Illegal importation of firearms for use in traffic and commission of other crimes.

 

Theoretical Perspectives There is a little scientific evidenced for the assertion that drug abuse cause crime. Writers on the subject have suggested that: • Illegal drugs contribute to crime• Illegal drugs to hand in hand with crime• Crime is a lifestyle issue and therefore drug use does not lead to crime but is merely a manifestation of deviant behavior by the individual.• Crime is too complex a phenomenon to be related to a single factor. Instead a complex web of social, economic and psychological factors converge to induce deviant behavior.• Drugs can actually reduce anti-social behavior as not all drug use has violent outcomes.

Review of the Concept of the ‘Community Leader’ and its Relation to the ‘Drug Lord’ The term ‘Community Leader’ has traditionally been used in a ‘community development’ context and has been in associated with leadership within a given community based on membership of the Village Council or performance in business, politics or social spheres. The term “Drug Lord’ in the traditional sense refers to an individual who heads an illegal drug empire, as occurs in South America. Strictly speaking there are no ‘drug lords’ in Trinidad and Tobago. The connection between the two terms was the result of a specific set of circumstances undertaken by the administration in trying to develop solutions to the drug problem in a particular area in Trinidad, Laventille. To complicate the issue, in Laventille they speak of the ‘Elders’ who are the de facto ‘community leaders’ of the area. Therefore, the connection is a tenuous one although it is possible for a local version of the ‘drug lord’ to become a ‘community leader’. Drug users use the term ‘drug pusher’ interchangeably with the ‘drug lord’ which suggests that the connection between these two terms is stronger than ‘community leader’.

Strategic Framework for Drug Demand Reduction in Trinidad and Tobago

Strategic Framework A strategic framework provides a strategic perspective on what should be done, why it should be done, and how it should be done. It sets out the key elements which provide a reference or benchmark against which the activities of relevant national programmers should be assessed. It should build on elements of the country’s strategic foundation for drug abuse prevention, including its mission and vision and the strategic goals that are being articulated. The framework should also define our core objectives as well as our intermediate-level expected outcomes.

Core Elements of the Strategic Framework Indication of core elements for a strategic framework emerged, when they were not actually articulated by key personnel and experts in the field.

Strategic Objectives Specific strategic objectives gleaned from observation and from the concerns and insights of members of the NDC were: 1. Identify a vision for the future consistent with national development plans.2. Reach and engage the non-traditional actors in order to enrich the demand reduction effort by broadening and deepening participation.3. Improve networking among individuals, agencies and institution to achieve greater consistency, improved capability and effective collaboration.4. Strive to have the notion of accountability embedded in the culture of the demand reduction activity.

Analysis Despite the measures taken and efforts made the drug abuse appear to be continuing unabated. Conclusions are that the situation is influenced significantly by the strength of the demand for the illegal substances, a scenario that requires new and more effective and productive responses. Fundamental change in the way of country goes about its demand reduction business is necessary and it is advanced that ‘a paradigm shift’ that perceives the illegal drug question as a development issue is a most appropriate change. A paradigm shift is an intellectually violent revolution where one conceptual world view is replaced by another. Shifting the emphasis of the drug trade from merely a legal/health issue to the more inclusive development issue therefore require fundamental changes’. The desirable change must result in an ‘end state’ which should be congruent with the declared vision of 2020. End state conditions would manifest themselves in healthy communities throughout the Nation.

Critical ThoughtsThe Role of the National Drug Council Strategic leadership, which Caldwell (q2993) describes as the capacity to take charge of one’s own, is the responsibility of the NDC. The NDC must undergo some transformation in its administrative and organizational structure to give it the best chance of meeting the challenge. Elements of an Appropriate Framework for Demand Reduction. The element of the framework below are categorized into a strategic objective (a vision), strategic priorities (core strategies), and action plans.

Strategic objectives Tangible elements of the emerging vision include:Communities where people can live in peace, feel secure, confident of afuture of sustainable prosperity.

ii. Information of drug use that is relevant, and current and easily accessible.– Using state-of-the-art technology.iii. Partnerships that cross sectors, institutions, boundaries and perspectives. Some key partners include the protective service, education authorities, the universities, the media, Ministry of Sport and Youth Affairs, the religious sector, arts & culture, business, labor, the judiciary, health, women’s organization.

Action Plans Many of these actions represent initiatives already being undertaken but together with new ideas they have the potential to support most of the core strategies described above. This draft strategic framework can serve as a road map for the journey towards the strategic goal of healthy communities. It should be considered a significant element of the country’s national development, a work in progress, all inclusive, transcending perceived boundaries, discovering new ways to move forward, collaborating, pooling resources and joining forces to attain the prosperous and sustainable future that is envisaged.