Adderall: Characteristics, Therapeutic Action, Applications for People With ADHD

Clinical Background

The drug Adderall is an a-methylphenethylamine, better known as amphetamine. Amphetamine as a drug can be dated back to the 1800s when a chemist found a chemical compound within a plant found in China. Barger and Dale discovered amphetamine in 1910 but a synthesized molecule for the drug that could be used for pharmaceutical purposes was created in 1927 by a chemist named G. A. Alles when he was looking to synthesize another drug.1 The company Smith, Kline and French introduced the initial form of amphetamines known as Benzedrine in 1935 as a treatment for narcolepsy, mild depression, as well as post-encephalitic Parkinsonism.1

In 1937, C. Bradley discovered the effects of amphetamines on children with behavioral problems.2 It was not until the 1970s when clinical trials were used to see the drug’s effectiveness on ADHD. Adderall and Adderall XR (extended release) had previously been approved for safe use as Obetrol but after Richwood Pharmaceuticals took over the company the name and product was changed to Adderall in 1994 and was then approved by the FDA in February of 1996.3 According to the Federal register the FDA had become aware that Adderall had been placed on a list of drugs that were no longer being marketed. However, after reviewing the list and information that was provided to them, they found that Adderall was not withdrawn for health-related reasons or for its effectiveness.4

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Adderall is considered a central nervous system stimulant. According to the DEA and their drug scheduling, Adderall is considered a Schedule II because it is considered a drug that has a high potential for abuse or lead to dependence.5 Other drugs that are also recognized as a central nervous stimulant would be Methamphetamines, Cocaine, Caffeine, Ephedrine.5

Pharmacological and Pathological Aspects

Adderall is the brand name that is used but it also comes as a generic drug as well, but Adderall XR does not have a generic brand. The generic brands are amphetamine and dextroamphetamine. Adderall is prescribed for Attention Deficit Hyperactivity Disorder or ADHD. This influences the nervous system, targeting the brain, that interferes with a person’s functioning and development.6 Children and adults that suffer from ADHD usually have an act of inattention, bouts of hyperactivity and are impulsive.

Inattention in a patient can cause their minds to wander, have a hard time focusing on tasks, and are disorganized. Hyperactivity can cause a patient to be fidgety, tap, make noises, or in constant movement, whether that be walking around, moving fingers, or talking. The impulsiveness can cause a patient to make quick decisions without thinking about the consequences, that it could cause them harm, or for instant gratification.6

When diagnosing and prescribing Adderall, primary care physicians, psychiatrists, pediatricians and child psychologists are the usual groups that take care of that. The patients will either have their scripts sent to their preferred pharmacy or the doctor will give hard copies of the prescription to the patient to take to their pharmacy. Depending on the dose, Adderall is usually taken once or twice a day, usually in the mornings to get the patient through the day and then early afternoon to get the patient through the rest of the day.

Refills are not permitted. The patient must have a doctor visit to get the next month’s prescription. As mentioned before Adderall is a Schedule II central nervous system stimulant. Adderall is given this classification because it has a high risk of being abused and can lead to dependence. Adderall is usually advertised to adults with ADHD whereas Ritalin is advertised to children.

Adderall is a drug that needs a prescription but there are other ways that it can be bought. Not only is Adderall prescribed by a doctor, but it is also sold on the black market as well as by drug dealers and even students. Adderall is marketed as a drug that will help one focus better however it is widely known throughout college age kids as the study drug.

Shire US Inc., has put out ads in newspapers with slogans such as “I’m depressed”, and giving statistics about people with ADHD being two times more likely to be divorced. They even brought out a campaign using Adam Levine, the lead singer of Maroon 5, to be the spokesman. According to an article by the Business Insider, it stated that since the year 2000 the FDA has gone after and cited every major company that makes ADHD drugs for misleading advertising which has caused people to worry that they may have ADHD and even have worse problems due to having ADHD.

Performance

Due to Adderall being a stimulant, the NCAA has placed it on the banned substance list. Since Adderall is a banned substance it can show up in a drug test and will cause an athlete to be suspended unless the athlete has filled out the medical exception documentation reporting form found on their website or provided by the institution that the athlete is attending.8 Once this is filled out if the athlete was to test positive during a drug test then there is proof that the athlete is being prescribed Adderall and is being treated by a physician for their diagnosis.

If an athlete is suspected of abusing Adderall, then the athletic director will be notified, and the athlete will be contacted and required to take a drug test. If the test is positive, then the athlete will be suspended from competition for an allotted time deemed necessary by the NCAA. The first positive test will be anywhere from half of the season to 365 days from the test date. A second positive test will result in a full year to loss of remaining eligibility.

Even though Adderall is a prescribed drug it can be abused and overused. There are not many case studies of the effects of Adderall in athletics but if an athlete becomes dependent on Adderall it can inadvertently harm the athlete and cause their performance to struggle. So, Adderall can be both, performance enhancing and performance decreasing. Due to the stimulant effect of the drug, Adderall can be a performance enhancer because it allows the athlete to have a heightened focusing capability while in competition.

Composition/Formation and Structure/Nomenclature

Adderall is a combination of amphetamine and dextroamphetamine. Dextroamphetamine is an isomer of amphetamine. This means that both drugs have the same chemical formula, makeup and number of atoms but the atoms are arranged in a different sequence than the other. The chemical formula for Adderall is C9H13N (see figure 1).10 Adderall is in the drug class of central nervous system stimulants.

Adderall is in the form of a salt. Adderall’s has a structure that is made up of a benzene aromatic ring and is bonded to an amine side group.12 Its active ingredients are composed of Dextroamphetamine Saccharate, Amphetamine Aspartate Monohydrate, Dextroamphetamine Sulfate, USP, Amphetamine Sulfate, USP.

The inactive ingredients of Adderall consist of Lactitol, Microcrystalline Cellulose, Colloidal Silicon Dioxide, Magnesium Stearate.13 The inactive ingredients of Adderall do not contribute to a different ingredient or to a side effect.

Absorption, Distribution, Metabolism and Excretion (ADME)

When Adderall is taken it is absorbed within the GI tract quickly and the effects can last from four to twenty-four hours. Adderall is then distributed throughout the body with most of the concentration within the brain and cerebral spinal fluid. The metabolism of Adderall takes place within the liver. Metabolism takes place in the liver and is caused by aromatic hydroxylation, N-dealkylation and deamination.10 Adderall is excreted from the body in multiple ways.

First is the urine where Adderall can be seen within the first three hours after taking it and within the first 12 hours an equal amount of both isomers within the drug have been excreted.10 If the urine pH is normal, then about half of the dose can be recovered in the urine as a derivative of alpha-hydroxy-amphetamine and only about 30%-40% of the urine can recover amphetamines. The determination of how much of the amphetamines that can be recovered all depends on the pH level of the urine. Second is in a person’s sweat and last is through human milk.10

Adderall consists of d-amphetamine and l-amphetamine salts that have a ratio of 3:1. Peak plasma concentration is around three hours after administering the dose. The half-life of Adderall is broken down due to both isomers with d-amphetamine being between 9.77-11 hours and l-amphetamine being between 11.5-13.8 hours. When it comes to children the average half-life is between 9-11 hours and between 10-13 hours in adults.10

Mechanism of Action

Adderall causes norepinephrine to be released and in larger doses it can cause a release of dopamine into the body by targeting their neurotransmitters within the brain. Effects of Adderall can inhibit monoamine oxidase and may act on the central 5-HT receptors. There is belief that noradrenaline can be released from alpha and beta receptors.10 According to a study by Daberkow it shows that an amphetamine dose is important in knowing its immediate effects. It showed that in low concentrations it acts like a blocker and like a releaser when there are higher doses.14

Adderall consists of amphetamines which are small molecules which allows it to pass through the blood brain barrier to affect the CNS. When it comes to diet Adderall can be influenced by the food that we eat. Since Adderall is a stimulant, depending on the pH of food that is consumed can decrease the effectiveness of the drug. GI acidifying agents which can lower the rate of absorption and urinary acidifying agents are groups that can lower the efficacy of amphetamines. The opposite tends to happen when GI alkalinizing agents and urinary alkalinizing agents increasing the actions of amphetamines.15

Therapeutic Applications/Effects

Adderall is most effective for patients that suffer from attention deficit hyperactive disorder (ADHD). Although it has been primarily used to treat ADHD, Adderall has been shown to be effective to help with daytime fatigue from narcolepsy.10 The therapeutic application, when it comes to ADHD allows for a stabilizing effect when it comes to a behavior issue within children who have issues with moderate to severe distractibility, short attention p, hyperactivity, emotional lability, and impulsivity.10 When a patient is taking Adderall, it helps to alleviate the symptoms of distractibility, hyperactivity, and impulsivity. The effects of Adderall allow a patient to function normally and focus on tasks that would have otherwise been difficult for them if they were not taking the medication.

When discontinued use of Adderall is needed for a patient depending on how long they have used the drug as well as if they were dependent on it. If the patient was dependent, then there could be withdrawal from the drug as the patient is discontinuing use. A weaning process may be necessary for the patient to discontinue use and a doctor should be consulted and involved during the process. Use of Adderall is not recommended to be discontinued abruptly due to withdrawal effects.16 Adderall is normally used by itself and not used in combination with any other drug.

Adverse Effects/Contraindications/Drug Interactions

Although Adderall is great drug that helps with attention deficit hyperactive disorder and narcolepsy there are adverse effects that can occur. These can include high risk for potential abuse, nervousness, insomnia (unable to sleep), irritability, talkativeness, changes in libido, dizziness, headaches, increased motor activity, chilliness, pallor or flush, blurred vision, mydriasis, and hyperexcitability and possible sudden death. There are also reasons that Adderall should not be taken by a patient and these include; advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, hypersensitivity or idiosyncrasy to the sympathomimetic amines, patients with a history of drug abuse and glaucoma.

Adderall has some negative drug interactions such as; acidifying agents which lower blood levels and the efficacy of amphetamines, adrenergic blockers are inhibited by Adderall, tricyclic antidepressants can cause striking and sustained heightened concentration, serotonergic drugs can cause the patient to be at risk for serotonin syndrome if paired with Adderall, hypertensive crisis can occur if MAO inhibitors are used with Adderall, amphetamines can counteract the effect of antihistamines.

Precautions for Adderall are that amphetamines can cause the patient to become dizzy and have a problem operating machinery or vehicles, patient medications guides can be given to provide the patient with everything about Adderall the patient needs. If you are allergic to Adderall or any other drugs within inform your doctor or pharmacist. Heart related problems like sudden death in patients who have heart problems or defects, stroke and heart attack in adults, increased blood pressure and heart rate.

Calling your doctor is necessary as soon as your child shows signs of chest pain, shortness of breath or fainting after taking Adderall. Possible mental/psychiatric problems. Patients should call their doctors if they or their children show signs of new or worsening mental symptoms while on Adderall, especially if seeing or hearing things that are not real. Possible circulation issues in the extremities where the fingers or toes are to feel numb, cool, painful or change color.

Conclusion

The information in this paper is useful to professionals such as primary care providers, neurological specialists, and pediatricians and beneficial to pediatric patients or adults who suffer from attention deficit hyperactivity disorder who would have difficulties with focusing on regular tasks and school activities. Patients that live active lifestyles have seen some decrease in symptoms of ADHD but do not mask all the symptoms or cause the disability to completely go away.

Informing the patient information on what the Adderall does, how it affects the body, what possible side affects are, contraindications and indications are all important things that the patient should know before starting to take Adderall or before they begin to give it to their children. Adderall is an important substance because there are many people who suffer from ADHD and many of them have been prescribed Adderall to assist them in their daily lives. Adderall helps to keep the patient focused so that daily tasks can be completed without distractions.

References

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2. History of Amphetamines. Amphetamines.com. http://amphetamines.com/history/. Accessed February 22, 2018.
3. Adderall New FDA Drug Approval | CenterWatch. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/59/adderall-mixed-salts-of-a-single-entity-amphetamine. Accessed February 23, 2018.
4. Determination That Adderall (Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine Saccharate; Dextroamphetamine Sulfate) Tablet and 13 Other Drug Products Were Not Withdrawn from Sale for Reasons of Safety or Effectiveness. Federal Register. https://www.federalregister.gov/documents/2013/11/12/2013-26856/determination-that-adderall-amphetamine-aspartate-amphetamine-sulfate-dextroamphetamine-saccharate. Published November 12, 2013. Accessed March 18, 2018.
5. Drug Schedules. DEA / Drug Scheduling. https://www.dea.gov/druginfo/ds.shtml. Accessed April 18, 2018.
6. Attention Deficit Hyperactivity Disorder. National Institute of Mental Health. https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml. Published March 2016. Accessed March 18, 2018.
7. Feloni R. These Are the Ridiculous Ads Big Pharma Used to Convince Everyone They Have ADHD. Business Insider. http://www.businessinsider.com/adhd-medication-marketing-techniques-2013-12. Accessed April 21, 2018.
8. ADHD Medical Exception Reporting Form. NCAA.org - The Official Site of the NCAA. http://www.ncaa.org/sites/default/files/2017SSI_ADHD_ReportingForm_20170829.pdf. Published December 6, 2017. Accessed February 22, 2018.
9. rpowell. NCAA Drug Testing Program. NCAA.org - The Official Site of the NCAA. http://www.ncaa.org/sport-science-institute/ncaa-drug-testing-program. Published July 20, 2016. Accessed February 23, 2018.
10. Pubchem. Amphetamine. https://pubchem.ncbi.nlm.nih.gov/compound/3007. Accessed February 23, 2018.
11. Modafinil vs Adderall - A Side-By-Side Comparison. FocusWish. http://www.focuswish.com/modafinil-vs-adderall/. Published November 7, 2016. Accessed March 18, 2018.
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13. FDA. Adderall. FDA access data. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011522s040lbl.pdf. Accessed February 22, 2018.
14. Calipari ES, Ferris MJ. Amphetamine Mechanisms and Actions at the Dopamine Terminal Revisited. J Neurosci. 2013;33(21):8923-8925. doi:10.1523/JNEUROSCI.1033-13.201Can Foods, Acids, and Antacids Interfere with Stimulants? ADHD Roller Coaster with Gina Pera. May 2017. https://adhdrollercoaster.org/medication/can-foods-acids-and-antacids-interfere-with-stimulants/. Accessed April 21, 2018.
15. How to Detox, Taper, or Wean Off Adderall. American Addiction Centers. https://americanaddictioncenters.org/adderall/how-to-quit/. Accessed March 18, 2018

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