The mechanism of action of ethanol

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Ministry of health of Ukraine

National university of pharmacy

Department of pharmacology

ESSAY

On the topic: Ethanol

Prepared by 3 rd year student, group 13

Ayoob Abdulkadhim

Kharkov - 2013

Introduction

When an alcoholic beverage is consumed it passes down the esophagus through the stomach and into the small intestine. Although a small amount of alcohol is absorbed into the bloodstream through the mucous membrane, the vast majority of alcohol enters the bloodstream through the walls of the small intestine. Alcohol is water soluble and the bloodstream rapidly transports the ethanol throughout the body where it is absorbed into the body tissues in proportion to their water content. ethanol alcohol sexy

Ethanol is greatly diluted by the body fluids. For example, a 1-ounce shot of 80-proof whiskey, which contains 0.4 fluid ounces of ethanol will be diluted ina 150-pound human, producing somewhere in the neighborhood of an 0.02% blood alcohol concentration. With a user that is smaller with say one half of the water weight in his or her body than the individual in the prior example, that same 0.4 fluid ounce of ethanol would likely produce an alcohol concentration ator near 0.04%.

Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a solvent, and as a fuel. In common usage, it is often referred to simply as alcohol or spirits.

Ethanol is a straight-chain alcohol, and its molecular formula is C2H5OH. Its empirical formula is C2H6O. An alternative notation is CH3-CH2-OH, which indicates that the carbon of a methyl group (CH3-) is attached to the carbon of a methylene group (-CH2-), which is attached to the oxygen of a hydroxyl group (-OH). It is a constitutional isomer of dimethyl ether. Ethanol is often abbreviated as EtOH, using the common organic chemistry notation of representing the ethyl group (C2H5) with Et.

The fermentation of sugar into ethanol is one of the earliest organic reactions employed by humanity. The intoxicating effects of ethanol consumption have been known since ancient times. In modern times, ethanol intended for industrial use is also produced from ethylene.

Ethanol has widespread use as a solvent of substances intended for human contact or consumption, including scents, flavorings, colorings, and medicines. In chemistry, it is both an essential solvent and a feedstock for the synthesis of other products. It has a long history as a fuel for heat and light, and more recently as a fuel for internal combustion engines.

Topical application

Ethanol is widely used as a solvent both in the home and in industry. Consumers may be exposed to ethanol from its application as a constituent of many household and personal products, such as cosmetics, hairsprays, window cleaners, de-icers and certain pharmaceutical preparations. Most people have experienced skin contact with alcoholic solutions.

The safety of topical applications of ethanol is still a matter of debate, and there appears to be scientific evidence pointing in both directions. On the one hand, researchers came to the conclusion that the range of damage caused to the skin by the alcohol cannot and should not be ignored, although the deleterious effects of ethanol exposure on the skin may pale into insignificance compared to its effects on the liver, central nervous system, and other body systems after ingestion. On the other hand, scientific studies attributed ethanol for topical uses as safe per se. However, there appears to be at least some evidence, including epidemiological data, about mouthwash use, and data from animal experiments showing that ethanol on the skin or inside the oral cavity may cause harm if used chronically. Evaluation according to EU cosmetics legislation, and other acts about chemical safety should consider the chronic toxic and carcinogenic potential of ethanol. In this article, the safety of topical uses of ethanol will be evaluated by a critical review of the scientific literature.

Absorption and metabolism

Alcohol in the blood and tissues must be inactivated and excreted from the body. This process is initiated by altering the chemical structure of the alcohol in such a way as to promote its excretion. The transformation of the alcohol molecule into a chemically related substance that is more easily excreted from the body is called metabolism or detoxification.

In the case of ETOH, the alcohol is metabolized in the liver by the enzyme alcohol dehydrogenase, to acetaldehyde which causes dilatation of the blood vessels and, after accumulation, is responsible for the subsequent hangover which ensues. The acetaldehyde is subsequently metabolized by the enzyme aldehyde dehydrogenase to acetate, a substance very similar to acetic acid or vinegar. In fact, measurement of blood serum acetate levels may be an indicator of "problem or chronic drinking"

Certain drugs can inhibit the acetaldehyde dehydrogenase enzyme responsible for the second step in metabolizing ETOH. Inhibition of this enzyme causes an increase in the blood acetaldehyde levels. Some of these drugs are probably known to you. Antabuse is used for the treatment of alcoholism. People taking this drug can get very sick from ingesting just a small amount of ETOH. Chloral hydrate is a sleeping pill that when put into someone's drink is known as a "Mickey Finn". Some orally administered antidiabetic drugs like Diabinese also cause an "Antabuse-like" reaction and the inhalation of the solvent trichloroethylene can also increase the effects of ethanol.

The alcohol molecule is a small polar molecule with both lipophilic and hydrophilic characteristics. The amphipathic qualities of alcohol help to explain its pharmacokinetics within the body. The lipophilic qualities explain how alcohol is absorbed by passive diffusion across the cell membranes without the need for modification. The hydrophilic combined with the polar properties of the alcohol molecule explain how alcohol is completely soluble in water and thus has a similar volume of distribution to total body water (TBW).

Blood alcohol concentration (BAC) is determined by the various factors that affect the rate at which alcohol is absorbed, distributed, metabolised and excreted from the body. Following oral administration absorption and distribution determines the proportion and rate at which orally ingested alcohol reaches the blood and body tissues (bioavailability). As alcohol is a small water soluble molecule that can cross cell membranes, it is absorbed from both the stomach (20 %) and the upper small intestine (80 %). The rate of absorption varies significantly in both intraindividual and interindividual comparisons even after standardised conditions. This suggests that intraindividual variability is due to variation in gastrointestinal function (gastric emptying, intestinal transit time, and portal blood flow). The rate of gastric emptying has a significant impact on the speed at which alcohol is absorbed, because alcohol is absorbed much faster from the small intestine, than it is from the stomach. Factors which affect alcohol availability and gastric emptying will greatly influence the rate of absorption. For example, the consumption of alcohol with food inhibits absorption because approximately 20% of the ingested alcohol is oxidised before it can be absorbed. The speed of absorption is also influenced by variation in portal blood flow, because alcohol crosses the biological membrane by passive diffusion thus good blood flow will maintain the concentration gradient and promote absorption. Any stimulation of the sympathetic nervous system (e.g. emotional state or exercise) will reduce portal blood flow and gastric motility thus decreasing alcohol absorption. The type of drink consumed also plays a role. Drinks with alcohol content between 20-30% are absorbed quickest. Whereas drinks with a higher alcohol content are absorbed more slowly, because an alcohol content over 30% irritates the gastric mucosa increasing mucus secretion and decreasing gastric emptying. Thus drinks with an alcohol content above 30% can cause a faster rise in BAC if served diluted with a mixer, than if they are served without dilution. This is especially true if the mixer is a carbonated drink as this can also increase the rate of absorption .

Bioavailability

The bioavailability of alcohol is reduced by first pass metabolism (FPM). Oxidation of alcohol by gastric alcohol dehydrogenase (ADH) in the gastric mucosa accounts for a small proportion of FPM, but the majority occurs via oxidation by ADH in the liver hepatocytes. The proportion of alcohol that is absorbed, and escapes FPM enters the systemic circulation and is rapidly distributed throughout the body tissues via the blood plasma until equilibrium between the BAC and tissue concentration is reached. The time until equilibrim is dependent upon the permeability (water content), rate of blood flow and mass of the tissue, but is generally achieved within 1-2 hours.

The same amount of alcohol absorbed can affect different people in different ways. Differences in TBW will influence alcohol pharmacokinetics because it determines the volume of distribution available for alcohol distribution within the body. Alcohol is preferentially distributed in tissues with higher water contents and a good blood supply (e.g. brain and skeletal muscle). Body composition is therefore an important consideration in pharmacokinetic studies because both body size and composition will have a significant impact on the volume of distribution. Females generally have a proportionately smaller lean body mass and a smaller blood volume. The result is a lower volume of distribution and higher BAC when females ingest the same amount of alcohol as men. It has also been suggested that higher BAC may be due to lower FPM by gastric ADH in the gastric mucosa of females. This would increase the bioavailability of alcohol resulting in increased BAC. However, the ability of gastric ADH to metabolise significant amounts of alcohol has been questioned because its activity is 100 times lower then hepatic ADH and more recent studies have failed to support this finding.

Mechanism of action of ethanol on the CNS

Alcohol perturbs the balance between excitatory and inhibitory influences in the brain, resulting in anxiolysis, ataxia, and sedation. This is accomplished by either enhancing inhibitory or antagonizing excitatory neurotransmission. Although ethanol was long thought to act nonspecifically by disordering lipids in cell membranes, it now is believed that proteins constitute the primary molecular sites of action for ethanol. A number of putative sites at which ethanol may act have been identified, and ethanol likely produces its effects by simultaneously altering the functioning of a number of proteins that can affect neuronal excitability. A key issue has been to identify proteins that determine neuronal excitability and are sensitive to ethanol at the concentrations (5 to 20 mM) that produce behavioral effects. A number of ion channels in the CNS are sensitive to ethanol, including representatives of the ligand-gated and G protein-coupled receptor families and voltage-gated ion channels. The primary mediators of inhibitory neurotransmission in the brain are the ligand-gated -aminobutyric acid A (GABAA) receptors, whose function is markedly..."

Long term sexual effects of alcohol

Chronic alcohol abuse, or alcoholism, inevitably has a devastating effect on sexuality, including:

Erectile disorders and dysfunction in men

Loss of sexual desire, significant decrease in sexual arousal for men and women

Difficulty experiencing orgasm for men and women

Chronic alcohol abuse also results in a variety of problems that have secondary sexual effects. For example, people who are chronic abusers of alcohol may have fewer long term relationships, they may be less able to find or maintain sexual partners, and they may have social, health, and financial difficulties that make them less desired sexual partners.

What is unknown is the point at which these sexual effects are irreversible. There has been some research with long term alcoholic men that has suggested some men are able to regain erectile functioning after a period of time without alcohol. But how much time is needed, and what kinds of gains can be made are uncertain.

Alcohol intoxication

Alcohol intoxication (also known as drunkenness or inebriation) is a physiological state that occurs when a person or animal has a high level of ethanol (alcohol) in his/her blood.

Common symptoms of alcohol intoxication include slurred speech, euphoria, impaired balance, loss of muscle coordination (ataxia), flushed face, vomiting, reddened eyes, reduced inhibition, and erratic behavior. In severe cases, it can cause coma or death.

Toxicologists use the term “alcohol intoxication” to discriminate between alcohol and other toxins.

Acute alcohol intoxication results from a very high level of alcohol in the blood. This term is used by health care providers, often in emergencies.

Signs and symptoms

The signs and symptoms of alcohol poisoning include:

• confusion

• vomiting

• dangerous anger

• seizures (fits)

• slow breathing (fewer than eight breaths a minute)

• pale, bluish skin

• cold and clammy skin

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