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PHARMACOLOGY
-2
By G.RAGHAVENDER REDDY
(MBBS)stu, ZSMU
grreddy836@gmail.com
CONTENTS
Drug metabolism
Xenobiotic metabolism
Enzyme inhibitor
Pharmacognosy
Pharmacophore
Galenic formulation
Pharmacopoeia
Pharmaceutical formulation
Dosage form
Route of administration
Injection ( medicine )
Drug injection
Catheter
Medical inhalants
Drug metabolism
Drug metabolism is the metabolism of drugs, their biochemical modification or
degradation, usually through specialized enzymatic systems. This is a form of
xenobiotic metabolism. Drug metabolism often converts lipophilic chemical
compounds into more readily excreted polar products. Its rate is an important
determinant of the duration and intensity of the pharmacological action of drugs.
Drugs are almost all xenobiotics. Other commonly used organic chemicals are
also xenobiotics, and are metabolized by the same enzymes as drugs. This
provides the opportunity for drug-drug and drug-chemical interactions or
reactions.
Contents
Phase I reactions usually precede Phase II, though not necessarily. During these
reactions, polar bodies are either introduced or unmasked, which results in
(more) polar metabolites of the original chemicals. In the case of pharmaceutical
drugs, Phase I reactions can lead either to activation or inactivation of the drug.
Quantitatively, the smooth endoplasmic reticulum of the liver cell is the principal
organ of drug metabolism, although every biological tissue has some ability to
metabolize drugs. Factors responsible for the liver's contribution to drug
metabolism include that it is a large organ, that it is the first organ perfused by
chemicals absorbed in the gut, and that there are very high concentrations of
most drug-metabolizing enzyme systems relative to other organs. If a drug is
taken into the GI tract, where it enters hepatic circulation through the portal vein,
it becomes well-metabolized and is said to show the first pass effect.
Several major enzymes and pathways are involved in drug metabolism, and can
be divided into Phase I and Phase II reactions:
Phase I
Oxidation
Reduction
It should be noted that during reduction reactions, a chemical can enter futile
cycling, in which it gains a free-radical electron, then promptly loses it to oxygen
(to form a superoxide anion).
Hydrolysis
Phase II
Methylation
* methyltransferase
Sulphation
* Glutathione S-transferases
* Sulfotransferases
Acetylation
* N-acetyltransferases
* Amino acid N-acyl transferases
Glucuronidation
* UDP-glucuronosyltransferases
o Mercapturic acid biosynthesis
Various physiological and pathological factors can also affect drug metabolism.
Physiological factors that can influence drug metabolism include age, individual
variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal
flora, or sex differences.
In general, drugs are metabolized more slowly in fetal, neonatal and elderly
humans and animals than in adults.
Genetic variation (polymorphism) accounts for some of the variability in the effect
of drugs. With N-acetyltransferases (involved in Phase II reactions), individual
variation creates a group of people who acetylate slowly (slow acetylators) and
those who acetylate quickly, split roughly 50:50 in the population of Canada. This
variation may have dramatic consequences, as the slow acetylators are more
prone to dose-dependent toxicity.
Pathological factors can also influence drug metabolism, including liver, kidney,
or heart diseases.
See also
Xenobiotic metabolism
Xenobiotic metabolism is the set of metabolic pathways that modify the chemical
structure of xenobiotics, which are compounds foreign to an organism's normal
biochemistry, such as drugs and poisons. These pathways are a form of
biotransformation present in all major groups of organisms, and are considered
to be of ancient origin. These reactions often act to detoxify poisonous
compounds; however, in some cases, the intermediates in xenobiotic metabolism
can themselves be the cause of toxic effects.
However, the existence of a permeability barrier means that organisms were able
to evolve detoxification systems that exploit the hydrophobicity common to
membrane-permeable xenobiotics. These systems therefore solve the specificity
problem by possessing such broad substrate specificities that they metabolise
almost any non-polar compound. Useful metabolites are excluded since they are
polar, and in general contain one or more charged groups.
Phases of detoxification
Phases I and II of the metabolism of a lipophilic xenobiotic.
Phase I - modification
In phase I, a variety of enzymes acts to introduce reactive and polar groups into
their substrates. One of the most common modifications is hydroxylation
catalysed by the cytochrome P-450-dependent mixed-function oxidase system.
These enzyme complexes act to incorporate an atom of oxygen into nonactivated
hydrocarbons, which can result in either the introduction of hydroxyl groups or
N-, O- and S-dealkylation of substrates. The reaction mechanism of the P-450
oxidases proceeds through the reduction of cytochrome-bound oxygen and the
generation of a highly-reactive oxyferryl species, according to the following
scheme:
\mbox{NADPH} + \mbox{H}^+ + \mbox{RH} \rightarrow \mbox{NADP}^+ +
\mbox{H}_2\mbox{O} +\mbox{ROH} \,
Phase II - conjugation
Conjugates and their metabolites can be excreted from cells in phase III of their
metabolism, with the anionic groups acting as affinity tags for a variety of
membrane transporters of the multidrug resistance protein (MRP) family. These
proteins are members of the family of ATP-binding cassette transporters and can
catalyse the ATP-dependent transport of a huge variety of hydrophobic anions,
and thus act to remove phase II products to the extracellular medium, where they
may be further metabolised or excreted.
Endogenous toxins
Studies on how people transform the substances that they ingest began in the
mid-nineteenth century, with chemists discovering that organic chemicals such
as benzaldehyde could be oxidized and conjugated to amino acids in the human
body. During the remainder of the nineteenth century, several other basic
detoxification reactions were discovered, such as methylation, acetylation, and
sulfonation.
In the early twentieth century, work moved on to the investigation of the enzymes
and pathways that were responsible for the production of these metabolites. This
field became defined as a separate area of study with the publication by Richard
Williams of the book Detoxication mechanisms in 1947. This modern biochemical
research resulted in the identification of glutathione S-transferases in
1961,followed by the discovery of cytochrome P450s in 1962, and the realization
of their central role in xenobiotic metabolism in 1963.
Enzyme inhibitor
Enzyme inhibitors are molecules that bind to enzymes and decrease their activity.
Since blocking an enzyme's activity can kill a pathogen or correct a metabolic
imbalance, many drugs are enzyme inhibitors. They are also used as herbicides
and pesticides. Not all molecules that bind to enzymes are inhibitors; enzyme
activators bind to enzymes and increase their enzymatic activity.
The binding of an inhibitor can stop a substrate from entering the enzyme's active
site and/or hinder the enzyme from catalysing its reaction. Inhibitor binding is
either reversible or irreversible. Irreversible inhibitors usually react with the
enzyme and change it chemically. These inhibitors modify key amino acid
residues needed for enzymatic activity. In contrast, reversible inhibitors bind non-
covalently and different types of inhibition are produced depending on whether
these inhibitors bind the enzyme, the enzyme-substrate complex, or both.
Many drug molecules are enzyme inhibitors, so their discovery and improvement
is an active area of research in biochemistry and pharmacology. A medicinal
enzyme inhibitor is often judged by its specificity (its lack of binding to other
proteins) and its potency (its dissociation constant, which indicates the
concentration needed to inhibit the enzyme). A high specificity and potency
ensure that a drug will have few side effects and thus low toxicity.
Enzyme inhibitors also occur naturally and are involved in the regulation of
metabolism. For example, enzymes in a metabolic pathway can be inhibited by
downstream products. This type of negative feedback slows flux through a
pathway when the products begin to build up and is an important way to maintain
homeostasis in a cell. Other cellular enzyme inhibitors are proteins that
specifically bind to and inhibit an enzyme target. This can help control enzymes
that may be damaging to a cell, such as proteases or nucleases; a well-
characterised example is the ribonuclease inhibitor, which binds to ribonucleases
in one of the tightest known protein–protein interactions. Natural enzyme
inhibitors can also be poisons and are used as defenses against predators or as
ways of killing prey.
Contents
* 1 Reversible inhibitors
o 1.1 Types of reversible inhibitor
o 1.2 Quantitative description of reversible inhibition
o 1.3 Measuring the dissociation constants of a reversible inhibitor
o 1.4 Special cases
o 1.5 Examples of reversible inhibitors
* 2 Irreversible inhibitors
o 2.1 Types of irreversible inhibition
o 2.2 Analysis of irreversible inhibition
o 2.3 Special cases
o 2.4 Examples of irreversible inhibitors
* 3 Discovery and design of inhibitors
* 4 Uses of inhibitors
o 4.1 Chemotherapy
o 4.2 Metabolic control
o 4.3 Acetylcholinesterase inhibitors
o 4.4 Natural poisons
* 5 See also
* 6 References
* 7 External links
Reversible inhibitors
* In mixed inhibition, the inhibitor can bind to the enzyme at the same time as
the enzyme's substrate. However, the binding of the inhibitor affects the binding
of the substrate, and vice versa. This type of inhibition can be reduced, but not
overcome by increasing concentrations of substrate. Although it is possible for
mixed-type inhibitors to bind in the active site, this type of inhibition generally
results from an allosteric effect where the inhibitor binds to a different site on an
enzyme. Inhibitor binding to this allosteric site changes the conformation (i.e.,
tertiary structure or three-dimensional shape) of the enzyme so that the affinity of
the substrate for the active site is reduced.
* Mixed-type inhibitors bind to both E and ES, but their affinities for these two
forms of the enzyme are different (Ki ≠ Ki'). Thus, mixed-type inhibitors interfere
with substrate binding (increase Km) and hamper catalysis in the ES complex
(decrease Vmax).
When an enzyme has multiple substrates, inhibitors can show different types of
inhibition depending on which substrate is considered. This results from the
active site containing two different binding sites within the active site, one for
each substrate. For example, an inhibitor might compete with substrate A for the
first binding site, but be a non-competitive inhibitor with respect to substrate B in
the second binding site.
where the modifying factors α and α' are defined by the inhibitor
concentration and its two dissociation constants
\alpha = 1 + \frac{[I]}{K_{i}}
\alpha^{\prime} = 1 + \frac{[I]}{K_{i}^{\prime}}.
Special cases
* Uncompetitive inhibition occurs when the inhibitor binds only to the enzyme–
substrate complex, not to the free enzyme; the EIS complex is catalytically
inactive. This mode of inhibition is rare and causes a decrease in both Vmax and
the Km value.
As enzymes have evolved to bind their substrates tightly, and most reversible
inhibitors bind in the active site of enzymes, it is unsurprising that some of these
inhibitors are strikingly similar in structure to the substrates of their targets. An
example of these substrate mimics are the protease inhibitors, a very successful
class of antiretroviral drugs used to treat HIV. The structure of ritonavir, a
protease inhibitor based on a peptide and containing three peptide bonds, is
shown on the right. As this drug resembles the protein that is the substrate of the
HIV protease, it competes with this substrate in the enzyme's active site.
Enzyme inhibitors are often designed to mimic the transition state or intermediate
of an enzyme-catalysed reaction. This ensures that the inhibitor exploits the
transition state stabilising effect of the enzyme, resulting in a better binding
affinity (lower Ki) than substrate-based designs. An example of such a transition
state inhibitor is the antiviral drug oseltamivir; this drug mimics the planar nature
of the ring oxonium ion in the reaction of the viral enzyme neuraminidase.
Nonpeptidic protease inhibitor tipranavir
However, not all inhibitors are based on the structures of substrates. For
example, the structure of another HIV protease inhibitor tipranavir is shown on
the left. This molecule is not based on a peptide and has no obvious structural
similarity to a protein substrate. These non-peptide inhibitors can be more stable
than inhibitors containing peptide bonds, because they will not be substrates for
peptidases and are less likely to be degraded.
Irreversible inhibitors
Types of irreversible inhibition
Reaction of the irreversible inhibitor diisopropylfluorophosphate (DFP) with a
serine protease
As shown in the figure to the left, irreversible inhibitors form a reversible non-
covalent complex with the enzyme (EI or ESI) and this then reacts to produce the
covalently modified "dead-end complex" EI*. The rate at which EI* is formed is
called the inactivation rate or kinact. Since formation of EI may compete with ES,
binding of irreversible inhibitors can be prevented by competition either with
substrate or with a second, reversible inhibitor. This protection effect is good
evidence of a specific reaction of the irreversible inhibitor with the active site.
The binding and inactivation steps of this reaction are investigated by incubating
the enzyme with inhibitor and assaying the amount of activity remaining over
time. The activity will be decrease in a time-dependent manner, usually following
exponential decay. Fitting these data to a rate equation gives the rate of
inactivation at this concentration of inhibitor. This is done at several different
concentrations of inhibitor. If a reversible EI complex is involved the inactivation
rate will be saturable and fitting this curve will give kinact and Ki.
Special cases
Chemical mechanism for irreversible inhibition of ornithine decarboxylase by
DFMO. Pyridoxal 5'-phosphate (Py) and enzyme (E) are not shown. Adapted from
Not all irreversible inhibitors form covalent adducts with their enzyme targets.
Some reversible inhibitors bind so tightly to their target enzyme that they are
essentially irreversible. These tight-binding inhibitors may show kinetics similar
to covalent irreversible inhibitors. In these cases, some of these inhibitors rapidly
bind to the enzyme in a low-affinity EI complex and this then undergoes a slower
rearrangement to a very tightly bound EI* complex (see figure above). This kinetic
behaviour is called slow-binding This slow rearrangement after binding often
involves a conformational change as the enzyme "clamps down" around the
inhibitor molecule. Examples of slow-binding inhibitors include some important
drugs, such methotrexate, allopurinol,and the activated form of acyclovir.
New drugs are the products of a long drug development process, the first step of
which is often the discovery of a new enzyme inhibitor. In the past the only way to
discover these new inhibitors was by trial and error: screening huge libraries of
compounds against a target enzyme and hoping that some useful leads would
emerge. This brute force approach is still successful and has even been extended
by combinatorial chemistry approaches that quickly produce large numbers of
novel compounds and high-throughput screening technology to rapidly screen
these huge chemical libraries for useful inhibitors.
More recently, an alternative approach has been applied: rational drug design
uses the three-dimensional structure of an enzyme's active site to predict which
molecules might be inhibitors. These predictions are then tested and one of these
tested compounds may be a novel inhibitor. This new inhibitor is then used to try
to obtain a structure of the enzyme in an inhibitor/enzyme complex to show how
the molecule is binding to the active site, allowing changes to be made to the
inhibitor to try to optimise binding. This test and improve cycle is then repeated
until a sufficiently potent inhibitor is produced. Computer-based methods of
predicting the affinity of an inhibitor for an enzyme are also being developed,
such as molecular docking and molecular mechanics.
Uses of inhibitors
Enzyme inhibitors are found in nature and are also designed and produced as
part of pharmacology and biochemistry. Natural poisons are often enzyme
inhibitors that have evolved to defend a plant or animal against predators. These
natural toxins include some of the most poisonous compounds known. Artificial
inhibitors are often used as drugs, but can also be insecticides such as
malathion, herbicides such as glyphosate, or disinfectants such as triclosan.
Chemotherapy
The structure of sildenafil (Viagra)
The coenzyme folic acid (left) compared to the anti-cancer drug methotrexate
(right)
The structure of a complex between penicillin G and the Streptomyces
transpeptidase. Generated from PDB 1PWC.
The most common uses for enzyme inhibitors are as drugs to treat disease. Many
of these inhibitors target a human enzyme and aim to correct a pathological
condition. However, not all drugs are enzyme inhibitors. Some, such as anti-
epileptic drugs, alter enzyme activity by causing more or less of the enzyme to be
produced. These effects are called enzyme induction and inhibition and are
alterations in gene expression, which is unrelated to the type of enzyme inhibition
discussed here. Other drugs interact with cellular targets that are not enzymes,
such as ion channels or membrane receptors.
Drugs also are used to inhibit enzymes needed for the survival of pathogens. For
example, bacteria are surrounded by a thick cell wall made of a net-like polymer
called peptidoglycan. Many antibiotics such as penicillin and vancomycin inhibit
the enzymes that produce and then cross-link the strands of this polymer
together. This causes the cell wall to lose strength and the bacteria to burst. In
the figure, a molecule of penicillin (shown in a ball-and stick form) is shown
bound to its target, the transpeptidase from the bacteria Streptomyces R61 (the
protein is shown as a ribbon-diagram).
Acetylcholinesterase inhibitors
Natural poisons
Many natural poisons act as neurotoxins that can cause paralysis leading to
death and have functions for defence against predators or in hunting and
capturing prey. Some of these natural inhibitors, despite their toxic attributes, are
valuable for therapeutic uses at lower doses.[ An example of a neurotoxin are the
glycoalkaloids, from the plant species in the Solanaceae family (includes potato,
tomato and eggplant), that are acetylcholinesterase inhibitors. Inhibition of this
enzyme causes an uncontrolled increase in the acetylcholine neurotransmitter,
muscular paralysis and then death. Neurotoxicity can also result from the
inhibition of receptors; for example, atropine from deadly nightshade (Atropa
belladonna) that functions as a competitive antagonist of the muscarinic
acetylcholine receptors
Although many natural toxins are secondary metabolites, these poisons also
include peptides and proteins. An example of a toxic peptide is alpha-amanitin,
which is found in relatives of the death cap mushroom. This is a potent enzyme
inhibitor, in this case preventing the RNA polymerase II enzyme from transcribing
DNA. The algal toxin microcystin is also a peptide and is an inhibitor of protein
phosphatases. This toxin can contaminate water supplies after algal blooms and
is a known carcinogen that can also cause acute liver hemorrhage and death at
higher doses.
* 1 Introduction
o 1.1 Origin
* 2 Ethnopharmacology
* 3 Issues in phytotherapy
o 3.1 Constituents and drug synergyism
o 3.2 Herb and drug interactions
* 4 Natural products chemistry
* 5 Loss of biodiversity
* 6 Sustainable sources of plant and animal drugs
* 7 External links
* 8 References
Introduction
The word "pharmacognosy" is derived from the Greek words pharmakon (drug),
and gnosis or "knowledge". The term pharmacognosy was used for the first time
by the Austrian physician Schmidt in 1811. Originally - during the 19th century
and the beginning of the 20th century - "pharmacognosy" was used to define the
branch of medicine or commodity sciences ("Warenkunde" in German) which
dealt with drugs in their crude, or unprepared, form. Crude drugs are the dried,
unprepared material of plant, animal or mineral origin, used for medicine. The
study of these materials under the name pharmakognosie was first developed in
German-speaking areas of Europe, while other language areas often used the
older term materia medica taken from the works of Galen and Dioscorides. In
German the term drogenkunde ("science of crude drugs") is also used
synonymously.
* medical ethnobotany: the study of the traditional use of plants for medicinal
purposes;
* ethnopharmacology: the study of the pharmacological qualities of traditional
medicinal substances;
* the study of phytotherapy (the medicinal use of plant extracts); and
* phytochemistry, the study of chemicals derived from plants (including the
identification of new drug candidates derived from plant sources).
* Zoopharmacognosy, the process by which animals self-medicate, by
selecting and using plants, soils, and insects to treat and prevent disease.
* Pharmcognosy-Biotechnology, the synthesis of natural bioactive molecules
using biotechnology.
* Herbal interactions, the interactions of herbs with other drugs and body.
* Marine Pharmacognosy, the study of chemicals derived from marine
organisms.
Origin
The word Pharmacognosy had its debut in the early 19th century to designate the
discipline related to medicinal plants, it is derived from the Greek word
pharmakon meaning “a drug” and gnosco meaning “ to acquire a knowledge”
and as recorded by Dr. K Ganzinger.
Pharmacognosy is closely related to botany and plant chemistry and indeed, both
originated from the earlier scientific studies of medicinal plants.
As the late as the beginning of the 20th century, the subject had developed
mainly in the botanical side, being concerned with the description and
identification of drugs. Both in the whole state and in porodler, and with their
history. Commerce, collection, preparation, and storage. Such branches of
pharmacognosy are still of fundamental importance, particularly for
pharmacopoeial identification and quality control purposes, but rapid
development in other areas has enormously expanded the subject.
At the 9th congress of Italian society of pharmacognosy it was stated that current
return of phyto-therapy was clearly reflected by the increased market of such
products. In 1998 the later for Europe, reached a figure of $6 billion, with
consumption for Germany of $2.5 billion, France $1.6 billion and Italy $600 billion.
In the US, where the use of herbal products has never been as prevalent as in
continental Europe, the market for all herb sales reached a peak in 1998 of $700
billion. This welcomed the scientific investigation of a rigorous nature.
The plant kingdom still holds many species of plants containing substances of
medicinal value which have yet to be discovered. Large numbers of plants are
constantly being screened for their possible pharmacological value.
Ethnopharmacology
The major herbs that have caused interactions include St. Johns Wort, which will
counteract immunosuppressive drugs and interfere with digoxin and protease
inhibitors. A complete list can be found at:
http://www.herbological.com/images/SJW_table.pdf. The constituents of garlic,
peppermint and milk thistle have been shown to have effects on the CYP3A4
enzymes in vitro, but it is not clear whether these constituents will have the same
effect in vivo (humans).
Loss of biodiversity
Farnsworth for example, has found that 25% of all prescriptions dispensed from
community pharmacies in the United States from 1959 to 1980 contained active
ingredients extracted from higher plants. In some countries in Asia and Africa
80% of the population relies on traditional medicine (including herbal medicine)
for primary health care.Constituents of substances used by traditional healers,
have rarely been incorporated into modern medicine. Quinine, physostigmine, d-
tubocurarine, pilocarpine and ephedrine, have been demonstrated to have active
effects Knowledge of traditional medicinal practices is fast disappearing(?),
particularly in the Amazon, as native healers die out and are replaced by more
modern medical practitioners. Botanists and pharmacologists are racing to learn
these ancient practices[citation needed], which, like the forest plants they
employ, are also endangered
An explanation for some species loss is habitat lost due to invasive species
introduction. Herbalist David Winston has suggested that a high proportion of
nonnative species seen as invasive (kudzu, Japanese knotweed, mimosa,
lonicera, St. Johnswort and purple loosestrife) may be harvested for the domestic
herbal medicine market
As species face loss of habitat or overharvesting, there have been new issues to
deal with in sourcing crude drugs. These include changes to the herb from
farming practices, substitution of species or other plants altogether, adulteration
and cross-pollination issues. For instance, ginseng which is field farmed may
have significant problems with fungus, making contamination with fungicides an
issue. This may be remedied with woods grown programs, but they are
insufficient to produce enough ginseng to meet demand. The wildcrafted
echinacea, black cohosh and American ginseng often rely upon old growth root,
often in excess of 50 years of age and it is not clear that younger stock will have
the same pharmaceutical effect. Black cohosh may be adulterated with the related
Chinese actea species, which is not the same. Ginseng may be replaced by
ginseniodes from Jiaogulan which has been stated to have a different effect than
the full panax root
The problem may be exacerbated by the growth of pills and capsules as the
preferred method of ingesting medication as they are cheaper and more available
than traditional, individually tailored prescriptions of raw medicinals but the
contents are harder to track. Seahorses are a case in point: Seahorses once had
to be of a certain size and quality before they were accepted by practitioners and
consumers. But declining availability of the preferred large, pale and smooth
seahorses has been offset by the shift towards prepackaged medicines, which
make it possible for TCM merchants to sell previously unused juvenile, spiny and
dark-coloured animals. Today almost a third of the seahorses sold in China are
prepackaged.
The farming of plant or animal species, used for medicinal purposes has caused
difficulties. Rob Parry Jones and Amanda Vincent write:
Pharmacophore
A pharmacophore was first defined by Paul Ehrlich in 1909 as "a molecular
framework that carries (phoros) the essential features responsible for a drug’s
(=pharmacon's) biological activity" (Ehrlich. Dtsch. Chem. Ges. 1909, 42: p.17). In
1977, this definition was updated by Peter Gund to "a set of structural features in
a molecule that is recognized at a receptor site and is responsible for that
molecule's biological activity" (Gund. Prog. Mol. Subcell. Biol. 1977, 5: pp 117–
143). The IUPAC definition of a pharmacophore is "an ensemble of steric and
electronic features that is necessary to ensure the optimal supramolecular
interactions with a specific biological target and to trigger (or block) its biological
response".
Pharmacopoeia
Pharmacopoeia (literally, the art of the drug compounder), in its modern technical
sense, is a book containing directions for the identification of samples and the
preparation of compound medicines, and published by the authority of a
government or a medical or pharmaceutical society
The name has also been applied to similar compendia issued by private
individuals.
Contents
* 1 History
o 1.1 National Pharmacopoeia
o 1.2 International Pharmacopoeia
* 2 Preparations
* 3 See also
* 4 References
* 5 External links
History
The first work of the kind published under government authority appears to have
been that of Nuremberg in 1542; a passing student named Valerius Cordus
showed a collection of medical receipts, which he had selected from the writings
of the most eminent medical authorities, to the physicians of the town, who urged
him to print it for the benefit of the apothecaries, and obtained for his work the
sanction of the senatus.
Before 1542 the works principally used by apothecaries were the treatises on
simples by Avicenna and Serapion; the De synonymis and Quid pro quo of Simon
Januensis; the Liber servitoris of Bulchasim Ben Aberazerim, which described
the preparations made from plants, animals and minerals, and was the type of the
chemical portion of modern pharmacopoeias; and the Antidotarium of Nicolaus
de Salerno, containing Galenical compounds arranged alphabetically. Of this, last
work there were two editions in use — Nicolaus magnus and Nicolaus parvus: in
the later several of the compounds described in the large edition were omitted
and the formulae given on a smaller scale.
Until 1617 such drugs and medicines as were in common use were sold in
England by the apothecaries and grocers. In that year the apothecaries obtained
a separate charter, and it was enacted that no grocer should keep an
apothecary’s shop. The preparation of physicians’ prescriptions was thus
confined to the apothecaries, upon whom pressure was brought to bear to make
them dispense accurately, by the issue of a pharmacopoeia in May 1618 by the
College of Physicians, and by the power which the wardens of the apothecaries
received in common with the censors of the College of Physicians of examining
the shops of apothecaries within 7 m. of London and destroying all the
compounds which they found unfaithfully prepared. This, the first authorized
London Pharmacopoeia, was selected chiefly from the works of Mezue and
Nicolaus de Salerno, but it was found to be so full of errors that the whole edition
was cancelled, and a fresh edition was published in the following December. At
this period the compounds employed in medicine were often heterogeneous
mixtures, some of which contained from 20 to 70, or more, ingredients, while a
large number of simples were used in consequence of the same substance being
supposed to possess different qualities according to the source from which it
was derived. Thus crabs’ eyes (i.e., gastroliths), pearls, oyster-shells and coral
were supposed to have different properties. Among other ingredients entering
into some of these formulae were the excrements of human beings, dogs, mice,
geese and other animals, calculi, human skull and moss growing on it, blind
puppies, earthworms, etc. Although other editions of the London Pharmacopoeia
were issued in 1621, 1632, 1639 and 1677, it was not until the edition of 1721,
published under the auspices of Sir Hans Sloane, that any important alterations
were made. In this issue many of the ridiculous remedies previously in use were
omitted, although a good number were still retained, such as dogs’ excrement,
earthworms, and moss from the human skull; the botanical names of herbal
remedies were for the first time added to the official ones; the simple distilled
waters were ordered of a uniform strength; sweetened spirits, cordials and
ratifias were omitted as well as several compounds no longer used in London,
although still in vogue elsewhere. A great improvement was effected in the
edition published in 1746, in which only those preparations were retained which
had received the approval of the majority of the pharmacopoeia committee; to
these was added a list of those drugs only which were supposed to be the most
efficacious. An attempt was made to simplify further the older formulae by the
rejection of superfluous ingredients. In the edition published in 1788 the tendency
to simplify was carried out to a much greater extent, and the extremely compound
medicines which had formed the principal remedies of physicians for 2000 years
were discarded, while a few powerful drugs which had been considered too
dangerous to be included in the Pharmacopoeia of 1765 were restored to their
previous position. In 1809 the French chemical nomenclature was adopted, and in
1815 a corrected impression of the same was issued. Subsequent editions were
published in 1824, 1836 and 1851.
The first Edinburgh Pharmacopoeia was published in 1699 and the last in 1841;
the first Dublin Pharmacopoeia in 1807 and the last in 1850.
National Pharmacopoeia
The preparations contained in these three pharmacopoeias were not all uniform
in strength, a source of much inconvenience and danger to the public, when
powerful preparations such as dilute hydrocyanic acid were ordered in the one
country and dispensed according to the national pharmacopoeia in another. As a
result, the Medical Act of 1858 ordained that the General Medical Council should
publish a book containing a list of medicines and compounds, to be called the
British Pharmacopoeia, which would be a substitute throughout Great Britain and
Ireland for the separate pharmacopoeias. Hitherto these had been published in
Latin. The first British Pharmacopoeia was published in the English language in
1864, but gave such general dissatisfaction both to the medical profession and to
chemists and druggists that the General Medical Council brought out a new and
amended edition in 1867. This dissatisfaction was probably owing partly to the
fact that the majority of the compilers of the work were not engaged in the
practice of pharmacy, and therefore competent rather to decide upon the kind of
preparations required than upon the method of their manufacture. The necessity
for this element in the construction of a pharmacopoeia is now fully recognized in
other countries, in most of which pharmaceutical chemists are represented on
the committee for the preparation of the legally recognized manuals.
There are national and international pharmacopoeias, like the EU and the US
pharmacopoeias. All the pharmacopoeias were issued under the authority of
government, and their instructions have the force of law in their respective
territories, except that of the United States, which was prepared by
commissioners appointed by medical and pharmaceutical societies, and has no
other authority, although generally accepted as the national textbook.
International Pharmacopoeia
Increased facilities for travel have brought into greater prominence the
importance of an approach to uniformity in the formulae of the more powerful
remedies, in order to avoid danger to patients when a prescription is dispensed in
a different country from that in which it was written. Attempts have been made by
international pharmaceutical and medical conferences to settle a basis on which
an international pharmacopoeia could be prepared, but due to national jealousies
and the attempt to include too many preparations nothing has yet been achieved.
Nonetheless, some progress has been made under the banner of the ICH (The
International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use:www.ich.org), a tri-regional
organisation that represents the drug regulatory authorities of the European
Union, Japan and the United States. Representatives from the Pharmacopoeias of
these three regions have met twice yearly since 1990 in the Pharmacopoeial
Discussion Group to try to work towards "compendial harmonisation"’. Specific
monographs are proposed, and if accepted, proceed through stages of review
and consultation leading to adoption of a common monograph that provides a
common set of tests and specifications for a specific material. Not surprisingly,
this is a slow process.
Preparations
The change occurred with the fourth edition of the British Pharmacopoeia in
1898. A committee of the Royal Pharmaceutical Society of Great Britain was
appointed at the request of the General Medical Council to advise on
pharmaceutical matters. A census of prescriptions was taken to ascertain the
relative frequency with which different preparations and drugs were used in
prescriptions, and suggestions and criticisms were sought from various medical
and pharmaceutical bodies across the British Empire. As regards the purely
pharmaceutical part of the work a committee of reference in pharmacy,
nominated by the pharmaceutical societies of Great Britain and Ireland (as they
were then), was appointed to report to the Pharmacopoeia Committee of the
Medical Council.
Some difficulty has arisen since the passing of the Adulteration of Food and
Drugs Act[citation needed] concerning the use of the Pharmacopoeia as a legal
standard for the drugs and preparations contained in it. The Pharmacopoeia is
defined in the preface as only "intended to afford to the members of the medical
profession and those engaged in the preparation of medicines throughout the
British Empire one uniform standard and guide whereby the nature and
composition of, substances to be used in medicine may be ascertained and
determined." It is obvious that it cannot be an encyclopaedia of substances used
in medicine, and can only be used as a standard for the substances and
preparations contained in it, and for no others. It has been held in the Divisional
Courts (Dickins v. Randerson) that the Pharmacopoeia is a standard for official
preparations asked for under their pharmacopoeial name. But there are many
substances in the Pharmacopoeia which are not only employed in medicine, but
have other uses, such as sulphur, gum benzoin, tragacanth, gum arabic,
ammonium carbonate, beeswax, oil of turpentine, linseed oil, and for these a
commercial standard of purity as distinct from a medicinal one is needed, since
the preparations used in medicine should be of the highest possible degree of
purity obtainable, and this standard would be too high and too expensive for
ordinary purposes. The use of trade synonyms in the Pharmacopoeia, such as
saltpetre for purified potassium nitrate, and milk of sulphur for precipitated
sulphur, is partly answerable for this difficulty, and has proved to be a mistake,
since it affords ground for legal prosecution if a chemist sells a drug of ordinary
commercial purity for trade purposes, instead of the purified preparation which is
official in the Pharmacopoeia for medicinal use. This would not be the case if the
trade synonym were omitted. For many drugs and chemicals not in the
Pharmacopoeia there is no standard of purity that can be used under the
Adulteration of Food and Drugs Act, and for these, as well as for the commercial
quality of those drugs and essential oils which are also in the Pharmacopoeia, a
legal standard of commercial purity is much needed. This subject formed the
basis of discussion at several meetings of the Pharmaceutical Society, and the
results have been embodied in a work entitled Suggested Standards for Foods
and Drugs, by C. G. Moor, which indicates the average degree of purity of many
drugs and chemicals used in the arts, as well as the highest degree of purity
obtainable in commerce of those used in medicine.
An important step has also been taken in this direction by the publication under
the authority of the Council of the Pharmaceutical Society of Great Britain of the
British Pharmaceutical Codex, in which the characters of and tests for the purity
of many nonofficial drugs and preparations are given as well as the character of
many glandular preparations and antitoxins that have come into use in medicine,
but have not yet been introduced into the Pharmacopoeia. This work may also
possibly serve as a standard under the Adulteration of Food and Drugs Act for
the purity and strength of drugs not included in the Pharmacopoeia and as a
standard for the commercial grade of purity of those in the Pharmacopoeia which
are used for non-medical purposes.
By the time phase III clinical trials are reached, the formulation of the drug should
have been developed to be close to the preparation that will ultimately be used in
the market. A knowledge of stability is essential by this stage, and conditions
must have been developed to ensure that the drug is stable in the preparation. If
the drug proves unstable, it will invalidate the results from clinical trials since it
would be impossible to know what the administered dose actually was. Stability
studies are carried out to test whether temperature, humidity, oxidation, or
photolysis (ultraviolet light or visible light) have any effect, and the preparation is
analysed to see if any degradation products have been formed.
Oral formulations
The way a drug is formulated can avoid some of the problems associated with
oral administration.
Tablet form
The disintegration time can be modified for a rapid effect or for sustained release.
Special coatings can make the tablet resistant to the stomach acids such that it
only disintegrates in the duodenum as a result of enzyme action or alkaline pH.
Pills can be coated with sugar, varnish, or wax to diguise the taste.
Capsule form
* Ointment - Combines oil (80%) and water (20%). Effective barrier against
moisture loss.
* Paste - Combines three agents - oil, water, and powder; an ointment in which
a powder is suspended.
* Powder
Dosage form
A dosage form (DF) is the physical form of a dose of a chemical compound used
as a drug or medication intended for administration or consumption. Common
dosage forms include pill, tablet, or capsule, drink or syrup, aerosol or inhaler,
liquid injection, pure powder or solid crystal (e.g., via oral ingestion or freebase
smoking), and natural or herbal form such as plant or or food of sorts, among
many others. Notably, the route of administration (ROA) for drug delivery is
dependent on the dosage form of the substance in question.
Various dosage forms may exist for a single particular drug, since different
medical conditions can warrant different routes of administration. For example,
persistent nausea and emesis or vomiting may make it difficult to use an oral
dosage form, and in such a case, it may be necessary to utilize an alternate route
such as inhalational, buccal, sublingual, nasal, suppository, or parenteral instead.
* 1 Types
o 1.1 Oral
o 1.2 Inhalational
o 1.3 Parenteral Injection
o 1.4 Topical
o 1.5 Suppository
* 2 See Also
* 3 References
* 4 External Links
Types
Oral
Inhalational
* Aerosol
* Inhaler
* Nebulizer
* Smoking (often in natural herb or freebase powder form (e.g., tobacco or
marijuana and cocaine or methamphetamine, respectively))
* Vaporizer (usually to vaporize natural herbs like marijuana)
Parenteral Injection
* Intradermal (ID)
* Intramuscular (IM)
* Intraosseous (IR)
* Intraperitoneal (IP)
* Intravenous (IV)
* Subcutaneous (SC)
Topical
Suppository
Route of administration
A route of administration in pharmacology and toxicology is the path by which a
drug, fluid, poison, or other substance is brought into contact with the body.
A substance must be transported from the site of entry to the part of the body
where its action is desired to take place (even if this only means penetration
through the stratum corneum into the skin). Using the body's transport
mechanisms for this purpose, however, is not trivial. The pharmacokinetic
properties of a drug (that is, those related to processes of uptake, distribution,
and elimination) are critically influenced by the route of administration.
Contents
* 1 Classification
o 1.1 Topical
o 1.2 Enteral
o 1.3 Parenteral by injection or infusion
o 1.4 Other parenteral
o 1.5 Other
* 2 Advantages and disadvantages
o 2.1 Inhalation
o 2.2 Injection
* 3 Uses
* 4 Notes
* 5 See also
* 6 References
* 7 External links
Classification
* topical: local effect, substance is applied directly where its action is desired.
* enteral: desired effect is systemic (non-local), substance is given via the
digestive tract.
* parenteral: desired effect is systemic, substance is given by routes other than
the digestive tract.
The U.S. Food and Drug Administration recognizes 111 distinct routes of
administration. The following is a brief list of some routes of administration.
Topical
* epicutaneous (application onto the skin), e.g. allergy testing, typical local
anesthesia
* inhalational, e.g. asthma medications
* enema, e.g. contrast media for imaging of the bowel
* eye drops (onto the conjunctiva), e.g. antibiotics for conjunctivitis
* ear drops - such as antibiotics and corticosteroids for otitis externa
* intranasal route (into the nose), e.g. decongestant nasal sprays. Nasal
administration can also be used for systemic effect. This is related to the
transmucosal route through a mucous membrane via insufflation.
* vaginal, e.g. topical estrogens, antibacterials
Enteral
Enteral is any form of administration that involves any part of the gastrointestinal
tract:
* by mouth (orally), many drugs as tablets, capsules, or drops
* by gastric feeding tube, duodenal feeding tube, or gastrostomy, many drugs
and enteral nutrition
* rectally, various drugs in suppository or enema form
Other parenteral
* transdermal (diffusion through the intact skin), e.g. transdermal patches such
as fentanyl in pain therapy, nicotine patches for treatment of addiction
* transmucosal (diffusion through a mucous membrane), e.g. insufflation
(snorting) of cocaine, sublingual, i.e. under the tongue, nitroglycerine, buccal
(absorbed through cheek near gumline), vaginal suppositories
* inhalational, e.g. inhalational anesthetics
* intracisternal: given between the first and second cervical vertebrae – used to
withdraw cerebrospinal fluid for dignostic purposes.
Other
[edit] Inhalation
Advantages
* Fastest method, 7–10 seconds for the drug to reach the brain
* User can titrate (regulate the amount of drug they are receiving)
Disadvantages
Injection
Advantages
* Fast: 15–30 seconds for IV, 3–5 minutes for IM and subcutaneous
* 100% bioavailability
* suitable for drugs not absorbed by the gut or those that are too irritant (anti-
cancer)
* One injection can be formulated to last days or even months, e.g., Depo-
Provera, a birth control shot that works for three months
* IV can deliver continuous medication, e.g., morphine for patients in
continuous pain, or saline drip for people needing fluids
Disadvantages
* Onset of action is quick, hence more risk of addiction when it comes to
injecting drugs of abuse
* Patients are not typically able to self-administer
* Belonephobia, the fear of needles and injection.
* If needles are shared, there is risk of HIV and other infectious diseases
* It is the most dangerous route of administration because it bypasses most of
the body's natural defenses, exposing the user to health problems such as
hepatitis, abscesses, infections, and undissolved particles or
additives/contaminants
* If not done properly, potentially fatal air boluses (bubbles) can occur.
* Need for strict asepsis
Uses
Some routes can be used for topical as well as systemic purposes, depending on
the circumstances. For example, inhalation of asthma drugs is targeted at the
airways (topical effect), whereas inhalation of volatile anesthetics is targeted at
the brain (systemic effect).
On the other hand, identical drugs can produce different results depending on the
route of administration. For example, some drugs are not significantly absorbed
into the bloodstream from the gastrointestinal tract and their action after enteral
administration is therefore different from that after parenteral administration. This
can be illustrated by the action of naloxone (Narcan), an antagonist of opiates
such as morphine. Naloxone counteracts opiate action in the central nervous
system when given intravenously and is therefore used in the treatment of opiate
overdose. The same drug, when swallowed, acts exclusively on the bowels; it is
here used to treat constipation under opiate pain therapy and does not affect the
pain-reducing effect of the opiate.
Enteral routes are generally the most convenient for the patient, as no punctures
or sterile procedures are necessary. Enteral medications are therefore often
preferred in the treatment of chronic disease. However, some drugs can not be
used enterally because their absorption in the digestive tract is low or
unpredictable. Transdermal administration is a comfortable alternative; there are,
however, only a few drug preparations are suitable for transdermal
administration.
Notes
Injection (medicine)
An injection (often referred to as a "shot") is an infusion method of putting liquid
into the body, usually with a hollow needle and a syringe which is pierced
through the skin to a sufficient depth for the material to be forced into the body.
An injection follows a parenteral route of administration, that is, administered
other than through the digestive tract.
Hypodermic syringe injection
* 1 Intramuscular injection
* 2 Depot injection
* 3 Hypodermic injections in nature
* 4 Injection pain
* 5 References
* 6 See also
* 7 External links
Intramuscular injection
Main article: Intramuscular injection
Depot injection
Various animals, and some plants, have been injecting for various reasons long
before humans began doing so. This process is often called stinging. Some
examples include:
Injection pain
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
sometimes injected, especially prescription opioids, since many 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,
thebaine and other codeine-based products also carry a moderate risk in this
case.[citation needed]
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 gangrene, tetanus, septicaemia,
thrombosis, embolism and all results thereof. Drug injection is also commonly a
component in HIV-related syndemics. Fragments from injection of pills are known
to clog the small blood vessels of the lungs, brain and elsewhere. Hitting arteries
and nerves is dangerous, painful, and presents its own similar spectrum of
problems.
Contents
* 1 History
* 2 Advantages
* 3 Disadvantages
* 4 Preparation of intravenous injection
* 5 Harm reduction
* 6 Safer injection of illicit drugs
* 7 Epidemiology
* 8 Alternatives to injection
* 9 See also
* 10 References
* 11 External links
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.
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 also means that the drug will have a very
strong and rapid onset (or rush).
* More efficient usage — Injection ensures that all of the drug will be absorbed.
* 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, the use of cotton to filter some drugs can lead to cotton fever.
The drug, usually in a powder or crystal form (though not always), is dissolved in
water, normally in a spoon. 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)[1] but is also used when pharmaceutical drugs
such morphine, OxyContin or Dilaudid are injected to better separate the drug
from the waxy filler; amphetamines lose potency when heated and cocaine HCl
(powdered cocaine) dissolves quite easily. Heroin prepared for the European
market is insoluble in water and usually requires the addition of an acidifier 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
break down the rock-like substance and form a liquid mixture. 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).
The preferred injection site is the crook of the elbow (i.e., the Median Cephalic
vein), on the user's non-writing hand. Other users opt to use the Basilic 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".
Harm reduction
Note that it is quite common for an IV user to use a single needle repeatedly or
share with other users. It's also quite uncommon for a sterilizing agent to be
used.
Compare this legitimate injection kit obtained from a needle-exchange program to
the user-compiled one above.
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, swabs, sterile water,
filter, tourniquet and a clean spoon or stericup. 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 option that people can take. 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.
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. Wheel filters are the most effective filters, however cotton
wool or tampons can be used, although to be more effective, several filtrations
should be undertaken.
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.
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 'hole' should face upward and be eased into the vein
at a 45 degree angle. 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’)
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
inadvertantly, or otherwise is extravasated), 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.
Epidemiology
Alternatives to injection
The safest alternative is, of course, not to take illicit drugs. The majority of legal
systems around the world encourage this option. Harm reduction acknowledges
that some people in a society will not choose this option and should at least be
provided information on safer means of taking illicit drugs to minimize the
individual health risks and the spread of viruses such as HIV and hepatitis C to
the wider community.
Drugs can also be smoked (e.g., tobbacco or marijuana alone or mixed with
heroin) or 'chased' (originating from 'chasing the dragon' - inhaling the vapors of
the heated drug). Smoking and chasing have negligible risk of bacterial or viral
transmission and the risk of overdose is lessened compared to injecting, but they
still retain much of the 'rush' of injecting as the effects of the drug occur very
rapidly. Chasing is a far safer way to use heroin than injecting, with the best
option being to use new aluminum foil, first passing a cigarette lighter flame over
both sides to help sterilize it.
Shebanging involves spraying the dissolved drug into the nose to be absorbed
by the nasal membrane.
Shafting, or rectal ingestion, relies on the many veins in the anal passage passing
the drug into the blood stream quite rapidly. Some users find that trading off
some of the 'rush' for fewer health risks is a good compromise. Shafting usually
involves about 1.5 ml of fluid mixed with the drug.
Women have the added option of shelving, where drugs can be inserted in the
vagina. This is similar to the rectum, in that there are many blood vessels behind
a very thin wall of cells, so the drug passes into the bloodstream very quickly.
Care should be taken with drugs such as amphetamine that may irritate the
sensitive lining of the rectum and vagina.
Catheter
In medicine a catheter is a tube that can be inserted into a body cavity, duct or
vessel. Catheters thereby allow drainage, injection of fluids or access by surgical
instruments. The process of inserting a catheter is catheterization. In most uses a
catheter is a thin, flexible tube ("soft" catheter), although in some uses it is a
larger, solid tube ("hard" catheter). A catheter left inside the body, either
temporarily or permanently, may be referred to as an indwelling catheter. A
permanently inserted catheter may be referred to as a permcath.
The ancient Syrians created catheters from reeds. "Katheter" originally referred
to an instrument that was inserted such as a plug. The word "katheter" in turn
came from "kathiemai" meaning "to sound" with a probe. The ancient Greeks
inserted a hollow metal tube through the urethra into the bladder to empty it and
the tube came to be known as a "katheter".
Contents
* 1 Uses
* 2 Inventors
* 3 Materials
* 4 Interventional procedures
* 5 References
* 6 See also
* 7 External links
Uses
* draining urine from the urinary bladder as in urinary catheterization, e.g., the
Foley catheter or even when the urethra is damaged as in suprapubic
catheterisation.
* drainage of urine from the kidney by percutaneous nephrostomy[1]
* drainage of fluid collections, e.g. an abdominal abscess
* administration of intravenous fluids, medication or parenteral nutrition with a
peripheral venous catheter
* angioplasty, angiography, balloon septostomy, balloon sinuplasty, catheter
ablation. Often the Seldinger technique is used.
* direct measurement of blood pressure in an artery or vein
* direct measurement of intracranial pressure
* administration of anaesthetic medication into the epidural space, the
subarachnoid space, or around a major nerve bundle such as the brachial plexus
* subcutaneous administration of insulin or other medications, with the use of
an infusion set and insulin pump
* A central venous catheter is a conduit for giving drugs or fluids into a large-
bore catheter positioned either in a vein near the heart or just inside the atrium.
* A Swan-Ganz catheter is a special type of catheter placed into the pulmonary
artery for measuring pressures in the heart.
* A Touhy borst adapter is a medical device used for attaching catheters to
various other devices.
* A Quinton catheter is a double or triple lumen, external catheter used for
hemodialysis.
Inventors
The modern application of the catheter was in use at least by 1868 when Dr.
N.B.Sornborger patented the Syringe and Catheter (patent #73402) with features
for fastening it to the body and controlling the depth of insertion.
David S. Sheridan was the inventor of the modern disposable catheter in the
1940s. In his lifetime he started and sold four catheter companies and was
dubbed the "Catheter King" by Forbes Magazine in 1988. He is also credited with
the invention of the modern "disposable" plastic endotracheal tube now used
routinely in surgery. Prior to his invention, red rubber tubes were used, sterilized,
and then re-used which often led to the spread of disease and also held a high
risk of infection. As a result Mr Sheridan is credited with saving thousands of
lives.
In the early 1900s, a Dubliner named Walsh and a famous Scottish urinologist
called Norman Gibbon teamed together to create the standard catheter used in
hospitals today. Named after the two creators, it was called the Gibbon-Walsh
catheter.
The Gibbon catheter and the Walsh catheter have been described and their
advantages over other catheters shown. The Walsh catheter is particularly useful
after prostatectomy for it drains the bladder without infection or clot retention.
The Gibbon catheter has largely removed the necessity of emergency
prostatectomy. It is also very useful in cases of urethral fistula. A simple
procedure such as dilatation of the urethra and passage of a Gibbon catheter
often causes the fistula to close. This catheter is also of use in the treatment of
urethral stricture and, as a temporary measure, in the treatment of retention of
urine caused by carcinoma of the prostate
Benjamin Franklin invented a flexible Catheter for his brother who had a bladder
stone.
Materials
A range of polymers are used for the construction of catheters, including silicone
rubber latex and thermoplastic elastomers. Silicone is one of the most common
choices because it is inert and unreactive to body fluids and a range of medical
fluids with which it might come into contact. On the other hand, the polymer is
weak mechanically, and a number of serious fractures have occurred in
catheters. It is widely used, for example, in breast implants where failures by
rupturing of the silicone shell are well attested. It is also used in Foley catheters
where fractures have been reported, often requiring surgery to remove the tip left
in the bladder.
Anaesthetics
* Desflurane
* Enflurane
* Ether
* Halothane
* Isoflurane
* Methoxyflurane
* Nitrous oxide
* Sevoflurane
Anti-Asthmatics/Bronchodilators
* Albuterol
* Arformoterol
* Beclomethasone
* Bitolterol
* Budesonide
* Budesonide/Formoterol
* Ciclesonide
* Cromolyn
* Dexamethasone
* Epinephrine
* Flunisolide
* Fluticasone
* Fluticasone/Salmeterol
* Formoterol
* Ipratropium
* Ipratropium/Albuterol
* Isoetharine
* Isoproterenol
* Levalbuterol
* Metaproterenol
* Mometasone
* Nedocromil
* Nitric oxide
* Pirbuterol
* Procaterol
* Racepinephrine (racemic epinephrine)
* Salmeterol
* Terbutaline
* Tiotropium
* Triamcinolone
Anti-Hypertensives
* Amyl nitrite
* Iloprost
Antimicrobials
* Pentamidine
* Ribavirin
* Tobramycin
* Zanamivir
Pulmonary surfactants
* Beractant
* Calfactant
* Colfosceril
* Exosurf
* Poractant
Miscellaneous
* Aromatic ammonia
* Dornase alfa
* Heliox
* Insulin
* Methacholine
* Nicotine
* Sodium chloride
Collected
By Gankidi
Raghavender
ZSMU