Therapeutic Index Essay Example
Therapeutic Index Essay Example

Therapeutic Index Essay Example

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  • Pages: 11 (3016 words)
  • Published: June 8, 2018
  • Type: Case Study
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The Inaba text discusses the relationship between the "therapeutic index" and the dangerous consequences of barbiturate addiction. The "therapeutic index" is especially significant in accidental overdoses, particularly involving barbiturates compared to other depressant drugs. Barbiturates are nonselective central nervous system (CNS) depressants that can cause various depressive effects, including mild sedation, hypnosis, general anesthesia, deep coma, and even death. The extent of CNS depression depends on factors such as how it is administered, dosage, and specific pharmacokinetic characteristics of the particular barbiturate.

Patient-specific factors, such as age, physical or emotional state, and concomitant use of other drugs, can influence the response to barbiturates. The exact mechanism of action of these drugs is not fully understood; however, they may increase and/or imitate the synaptic effects of gamma-amino butyric acid (GABA), which is an inhibitory neurotransmitter. Barbiturates' sedat


ive-hypnotic effects may occur because they can inhibit conduction in the reticular formation, thereby reducing impulses reaching the cerebral cortex. The anticonvulsant activity of barbiturates may be due to decreased synaptic transmission in the central nervous system (CNS) and an increased threshold for electrical stimulation in the motor cortex.

Phenobarbital is the only barbiturate that has anticonvulsant properties when given in lower doses that induce sleep. The therapeutic range of barbiturates is limited because the amounts needed to reduce anxiety and depress the central nervous system do not differ greatly. As a result, using barbiturates as anxiety medications usually results in some level of cognitive impairment.

Excessive consumption of a substance can lead to significant impairment in cognitive and physical abilities, resulting in impaired judgment, distorted perception, slurred speech, and coordination difficulties. However, it is important to note that certain individuals such a

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children and the elderly may initially experience paradoxical effects like temporary euphoria, excitement, elation, and confusion before eventually feeling drowsy.

Barbiturates have a higher addiction potential compared to heroin and present a greater risk to health. The withdrawal symptoms associated with barbiturates are even more perilous. On average, barbiturates cause over 3,000 deaths annually, with nearly half of these being suicides. Despite posing a significant issue in schools, barbiturates are still categorized as "soft" drugs since they can be legally obtained through a prescription. In the United States, around 300 tons of barbiturates are manufactured each year and can be found in one out of three medicine chests. There are 2,500 different varieties of barbiturates.

Out of the numerous synthesized drugs available, only around twelve are commonly used. In a recent year, the public spent $16 million on prescriptions for the top five barbiturate "sleepers," also known as sleeping pills, resulting in a total of nineteen million prescriptions. The drug industry produces ten billion doses of "downers" each year, which includes both barbiturates and nonbarbiturate sedative-hypnotics. This amounts to fifty doses per person in the United States, considering men, women, and children. Around one million individuals regularly misuse barbiturates. Barbiturates are depressants that impact the central nervous system and consist of either barbituric acid or malonylurea. These drugs can be classified into three categories: long-acting, short-to-intermediate-acting, and ultra-short-acting.

The long-acting drugs, such as Veronal (barbital), Luminal (pennobarbital), Mebaral (mephobarbital), and Gemonil (methabarbital), are used for treating epilepsy, controlling peptic ulcers, and managing high blood pressure. Additionally, there are short-to-intermediate-acting drugs with a duration of four to six hours that are often misused as sleeping pills or barbiturates. This

group includes Alurate (aprobarbital), Amytal (amobarbital), Butisol Sodium (butabarbital), Dial (diallybarbituric acid), Nembutal (pentobarbital), Seconal (secobarbital), and Tuinal (amobarbital and secobarbital). Furthermore, there are ultra-short-acting barbiturates that have an immediate but brief effect. These can be given intravenously as anesthetics or combined with inhalants like nitrous oxide for sedation. This category comprises Fentothal Sodium (thiopental), Brevital (sodium methohexital) and Suritall(sodium thiamylal).

Barbiturates, commonly employed for medical reasons, usually possess names ending in "al". Their purposes encompass inducing sleep, fostering relaxation, managing seizures, alleviating pain, reducing stress, and aiding individuals with alcoholism. Nonetheless, they are not appropriate for alleviating intense pain and may induce hyperalgesia - an intensified sensitivity to pain. Additionally, their efficacy as sleep aids diminishes over time due to tolerance development and they have the potential to disrupt REM sleep patterns, thereby potentially resulting in psychological repercussions.

Tranquilizers have replaced barbiturates in many areas, serving multiple purposes. Apart from their legitimate medical use, the production of extensive amounts of barbiturates satisfies the insatiable habits of "downer" abusers. The short-to-intermediate-acting versions are highly sought after due to their speedy and lasting effects. Popular examples include blue-capsuled Amytal (amies, blues, bluebirds, blue devils, blue heavens), red-capsuled Seconal (reds, pinks, redbirds, red devils, seccies), red-and-blue Tuinals (rainbows, tooies, double trouble), and yellow-capsuled Nembutal (yellows, nembies, yellow jackets, yellow bullets). Additionally, longer-lasting phenobarbitals like Luminal are extensively misused. Homemade pink capsules known as Mexican reds are sold on the streets; however, their content and potency are variable, making them hazardous.

Barbiturates are considered affordable when prescribed, with prices ranging from a penny to 15 cents each. However, their street value is higher. They are commonly available in various forms like

colorful capsules, tablets, suppositories, or as an injectable liquid. While oral ingestion is typically preferred due to the fast-acting nature of the capsules, some individuals known as "barb freaks" opt for mainlining to experience a more intense rush. Unfortunately, they often ignore potential risks such as severe infection and abscesses if the drug is mistakenly injected under the skin. It's important to note that hitting an artery can lead to gangrene and may require amputation of the affected area.

Barbiturates have a depressant effect on the central nervous system, inhibiting nerve signals in the brain and altering chemical balance. This results in decreased functioning of certain organ systems such as heart rate, blood pressure, respiration, and neurological activity. These drugs also cause relaxation of skeletal muscles. The potency of the drug increases with higher doses, leading to a slowdown of bodily functions ranging from anxiety relief to sedation, hypnosis, anesthesia, coma, and ultimately death.

Upon ingestion, barbiturates enter the bloodstream and are then distributed throughout the body. They tend to be most concentrated in fat deposits and organ tissues. Eventually, they are metabolized and eliminated by the kidneys and liver.

The onset of action of a drug is determined by how quickly it moves through the body and is metabolized. Laboratory tests can detect barbiturates in the body. The effects of the drug are influenced by factors such as dosage, type of barbiturate, metabolism, method of administration, and surrounding circumstances. These effects can vary from person to person and may also differ within the same individual.

Barbiturates, like alcohol, can produce different reactions from calmness to aggression by depressing the central nervous system. They have immediate effects that induce

a peaceful and relaxed state, relieving anxiety and stress. As one becomes intoxicated with barbiturates, concerns become less significant, leading to a blurred sense of importance.

The user may experience disorientation, impaired speech, weakened muscles, and significantly slowed response time in their altered reality. If they fall asleep, they may wake up with a hangover. Prolonged and regular use of barbiturates can cause ongoing symptoms such as constant drowsiness, decreased concentration and memory, coordination and perception problems, emotional instability, skin rashes, nausea, anxiety, nervousness, involuntary eye movements (nystagmus), unsteady walking (ataxia), slurred speech (dysarthria), and trembling hands (tremors). Barbiturate use can also result in paranoid delusions and increased aggression – both of which are commonly associated with barbiturates: violence.

The use of barbiturates, whether on their own or in combination with amphetamines, plays a significant role in drug-related assaults. In addition to this, continued usage results in tolerance, where larger doses are needed for the desired effects and dependence develops both physically and psychologically. Although tolerance increases gradually over time, the amount required for a lethal dose remains constant. As a result, individuals who regularly consume these drugs may require an extremely high dosage that can have potentially fatal consequences. Generally speaking, a lethal dose is considered to be ten times the prescribed amount for most people.

The typical therapeutic dosage of 100 to 200 mg per day does not lead to dependence rapidly. Nevertheless, individuals who consistently surpass the dosage of 600 mg a day for two months or 800 mg a day for one month will develop tolerance. Unlike opiates, tolerance towards this substance gradually builds up and may decrease after refraining from it for one

to two weeks. If high doses are consumed for three months or longer, addiction may arise and discontinuation will trigger withdrawal symptoms.

Withdrawal from barbiturates is more severe and life-threatening compared to heroin. If left untreated, sudden cessation can last up to two weeks with increasingly violent symptoms like loss of appetite, anxiety, insomnia, sweating, agitation, nausea, vomiting, hyperactivity, tremors, severe cramps, increased heart rate, and muscle twitches. These symptoms escalate over time to include hallucinations, delirium, paranoia,
high body temperature,
, and seizures resembling epileptic episodes. In some cases, alcoholic-like Delirium Tremens (DTs) may occur resulting in a psychotic state and even death due to exhaustion or cardiovascular collapse. The peak of untreated withdrawal symptoms occurs within 2-3 days for short-acting barbiturates and 7-8 days for long-acting ones. It's important to note that withdrawal should never be attempted alone.

Medical supervision is essential for ensuring safety during the withdrawal process, ideally within a hospital setting. The duration of medically supervised withdrawal varies based on the severity of addiction and typically takes several months. Initially, the addict continues to receive their usual dosage of intoxicant but gradually reduces it by 10 percent each day until they are drug-free. Additional support measures, including attentive diet and psychiatric assistance, are provided throughout this process.

Alcohol is often used as a substitute for barbiturates to alleviate withdrawal symptoms, as it has cross-tolerance with them. This substitution helps reduce the severe effects of barbiturate withdrawal. To achieve complete recovery, individuals battling addiction must maintain a balanced diet, intake vitamins and fluids, and receive long-term psychiatric care. Combining barbiturates with other depressant drugs increases their addictive potential.

When alcohol, opiates, tranquilizers, antihistamines, and nonbarbiturate hypnotic sedatives

are combined, the risk of overdose significantly increases. This combination has a synergistic effect on the central nervous system and can result in heart and respiratory system failure. It is crucial to emphasize the hazardous mixture of barbiturates and alcohol since alcohol intensifies the depressive effects of barbiturates and enhances their potency. This lethal combination is accountable for numerous annual fatalities.

When barbiturates are combined with alcohol, it can lead to an overdose. Due to the liver's focus on processing alcohol, barbiturates can freely travel throughout the body and cause harm to different organs. Those addicted to heroin often use barbiturates as a replacement when heroin is not accessible. Individuals undergoing methadone treatment may seek out depressants for a forbidden high that methadone maintenance cannot provide.

It is crucial to avoid mixing heroin with barbiturates as the majority of deaths from a heroin overdose are caused by using multiple drugs, including heroin, barbiturates, and alcohol. Combining amphetamines with barbiturates is extremely risky and considered one of the most dangerous forms of drug abuse. When taken together, like in the case of the amphetamine-barbiturate Dexamyl or when used alternatively for stimulation and sedation, these two drugs can lead to separate addictions. The combination produces an intensified sense of euphoria compared to using either drug individually.

Individuals addicted to speed frequently switch between using amphetamines to boost energy and barbiturates for relaxation. This hazardous cycle can result in fatal consequences for both the addict and those impacted by their ensuing psychosis. People with heart defects, low blood pressure, depression, or anxiety should refrain from depressant use. Additionally, pregnant women must avoid barbiturates, as they can cross the placental barrier

and cause addiction in infants born to addicted mothers.

Driving while influenced by barbiturates can be equally perilous as driving under the influence of alcohol if the dosage surpasses 100 mg. Illegally acquired downers frequently contain unidentified substances or toxins like arsenic or strychnine. Homemade capsules may appear legitimate, as it is easy to partially empty a capsule and refill it with a different powder. Each year, more than three thousand deaths occur due to barbiturate overdoses, with 42 percent being suicides and the rest either accidental from consuming deadly amounts or from combining them with other drugs such as alcohol. People who are already sedated may unknowingly consume lethal quantities due to their impaired memory, known as "drug automatism." Death is swift for those who overdose on short-acting barbiturates, whereas individuals who overdose on longer-acting downers typically pass away in hospitals.

Severe central respiratory depression is the typical reason for barbiturate fatality. Signs of an overdose include shock syndrome, characterized by sweaty, cold skin; a rapid, weak pulse; and either very slow or rapid, shallow breathing. Subsequently, deep coma ensues along with respiratory and kidney failure. Survivors of barbiturate overdose may experience brain damage due to reduced oxygen supply to the brain. It is crucial to seek medical assistance in a hospital setting for treating an overdose. However, in an emergency situation until professional help arrives, it is important to prevent the victim from falling asleep.

Encourage continuous walking and, if feasible, induce vomiting by stimulating the back of his throat. Refrain from offering coffee, as it can accelerate the absorption of barbiturates in the stomach. Additionally, refrain from administering amphetamines to the affected individual, as the

combination poses a potentially fatal risk.

Contrary to popular belief, the use of amphetamines does not counteract the effects of barbiturates. In cases of overdose, hospitalization may be necessary, including the procedure of stomach pumping. However, this approach is often ineffective as it does not sufficiently eliminate the drug from the body which has already been dispersed. Treatment for overdose also involves sustaining heart function, blood transfusions, oxygen administration, and kidney dialysis- the process of linking the affected individual to a kidney machine to cleanse their blood from the drug. The implementation of pharmacological methods such as stimulants, blood-pressure elevators, and diuretics to facilitate excretion remains a topic of controversy.

Some people believe that these agents add too much pressure to an already weakened system, thereby hiding important symptoms. Barbiturates were initially created in Belgium in 1684, but it wasn't until 1403 that the search for the perfect sedative-hypnotic was considered complete after the introduction of Veronal. Luminal, introduced in 1912, became the next popular barbiturate, followed by the synthesis of more than 2,500 derivatives of barbituric acid since then. The drug, which is tasteless, odorless, and easily prescribed and dispensed, initially appeared to be the ideal solution for anxiety and sleepless nights.

In the 1930s, evidence started to accumulate that this insomnia remedy had similar negative effects to alcohol. However, the associated warnings and publicity had the opposite effect, leading to barbiturates being known as "thrill pills" in the 1940s. Even though the risks of barbiturates are recognized today, little official action has been taken to prevent their misuse. The public and the government are convinced of the drug's safety due to misinformation, inadequate clinical testing,

incomplete labeling, and misleading promotional claims. Additionally, many individuals become legally introduced to the drug through tic prescriptions.

Easily accessible, whether through legitimate prescriptions, from acquaintances, or through illicit means, the drug is prevalent. Illegally manufactured barbiturates are produced within the United States by pharmaceutical companies, then transported to Mexico and smuggled back into the country. Short-acting barbiturates are currently categorized as Schedule If substances under the Comprehensive Drug Abuse Prevention and Control Act of 1970. Despite ongoing debates regarding their efficacy and risks, sleeping pills have not undergone formal reassessment by the FDA since 1969. While under appropriate medical supervision, barbiturates may be beneficial for certain individuals, the dangers associated with misuse and abuse cannot be overlooked.

Child of the drug industry; panacea of the 1970s-they have earned the name of "downers:" Two drugs that produce overtly similar effects will sometimes produce exaggerated or diminished effects when used together. A quantitative assessment is necessary to differentiate these cases from mere additive action. This differentiation is based on the classic pharmacologic definition of additivity, which briefly means that each constituent contributes to the effect according to its own potency. Thus, the relative potency of the agents, which may not be constant at all levels of effect, allows for a calculation using dose pairs to determine the equivalent of either agent and the effect by using the equivalent in the dose-response relation of the reference compound. The calculation is assisted by an isobologram, a popular graph that visually assesses the interaction but also requires independent statistical analysis.

The latter can be achieved by performing calculations that utilize the total dose in a fixed-ratio combination in addition to the calculated

total dose for the same effect. Various methods can be utilized, each applicable to experiments where a single drug is administered at two different sites. When deviations from additivity are observed in either "two-drug" or "two-site" experiments, this information can be valuable in designing further experiments to uncover mechanisms. Several examples, primarily from studies on analgesic drugs, demonstrate the practicality of this approach.

The introduction of a single drug (or site) puts it in potential contact with numerous chemicals already present in the system, emphasizing the significance of this topic in other areas of biological investigation. The concept of drug synergism is explained, along with a mention of the synergistic interaction between alcohol and other drugs. Moreover, one way in which alcohol could enhance the potentially lethal effects of drug-taking behavior is described. Drug Synergism refers to the enhancement of a drug's effectiveness or treatment, often achieved by combining it with another drug or agent. If two drugs with similar action, such as barbiturates and alcohol (both depressants), are taken together, an exaggerated effect may occur, exceeding the impact of each drug taken separately at the given dose.

The concept of combining substances can be illustrated by saying that 1+1=5. For instance, consider when a person consumes both alcohol and a barbiturate. Individually, these substances may not cause significant harm. However, when taken together, they can potentially lead to a coma or even death. It's important to note that alcohol is a type of depressant drug.

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