Methylphenidate (Concerta): Mechanism of Action

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Table of Contents

Introduction
Historical Background
Mechanism of Action
Pharmacokinetics
Pharmacotherapy
Interactions with psychotherapy
Conclusion
References

Introduction

Methylphenidate (MPH) is central nervous system stimulant, mainly administered to patients suffering from “attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), postural orthostatic tachycardia syndrome, narcolepsy and other off label cases such as lethargy, obesity, neural insult, depression, and obsessive compulsive disorder” (Multum 1). When consumed by a patient it stimulates a chemical reaction which finally makes the patient active. It should be administered alongside “a treatment program that is psychological, educational and social inclusive” (Multum, 2010, p.1).

Patients with trends of drug dependence or alcoholism should take this drug with a lot of caution since chronic abusive use can result to tolerance and psychological dependence, which is usually accompanied by abnormal behaviours of varying intensity such as Frank psychotic episodes. Withdrawal from abusive consumption should be cautiously supervised since it is mainly accompanied by severe depression. Also, withdrawal should be supervised keenly since it is likely to dispose symptoms of underlying issues that may require immediate attention (RxList, 2011).

Concerta may be found in the market bearing various brand names some of which include “Ritalin, Attenta, methylin, penid and Rubifen” (RxList, 2011, p. 1). The white powder is crystalline in nature, odourless and is acidic to the litmus paper. It has a molecular weight of 269.77 and dissolves completely in water, methanol and alcohol and partly in chroloform and acetone. Methylphenidate is manufactured from the following ingredients:

Butylated hydroxytoluene, carnauba wax, cellulose acetate, hypromellose, lactose, phosphoric acid, poloxamer, polyethylene glycol, polyethylene oxides, povidone, propylene glycol, sodium chloride, stearic acid, succinic acid, synthetic iron oxides, titanium dioxide, and triacetin. (RxList, 2011)

MPH has a short half-life, which calls for administration of several doses in a day, probably three times in a day. Individuals should first confirm whether they are allergic to MPH before consuming concerta. Patients who have used MAO inhibitor such as “Furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate)” (Multum, 2010, p. 1) within a fortnight should not use MPH since it can result to fatal side effects. Also, patients suffering from the following ailments should not take concerta:

Glaucoma, overactive thyroid, severe high blood pressure, Tourette’s syndrome, angina, heart failure, heart rhythm disorder, recent heart attack, a hereditary condition such as fructose intolerance, glucose-galactose mal-absorption, or sucrase-isomaltase deficiency, or severe anxiety, tension, or agitation. (Multum, 2010, p. 1)

Its pharmacological impacts have a close relationship with those of cocaine.

Historical Background

MPH’s first synthesis dates back to 1944 and was carried out by chemist Leandro Panizzon of Ciba Company for narcolepsy. MPH was later was later identified as a stimulant in 1954 and marketed in 1955 (Tone & Watkins, 2007, p134). Leandro’s efforts were triggered by his wife’s condition of low blood pressure. Rita was a tennis ball player and would take concerta tablets before going to the field in order to have her nerves stimulated. Leandro named the drug Ritalin after his wife. MPH was used in 1960’s for children treatment with cases of ADD and ADHD. It was first used as a mixture of two race mates, 80% erythro and 20% threo. Pharmacists’ later focused more on activating the erythro isomer.

Adverts dating back to 1950’s and 1960’s were commonly identified with tired patients whose conditions were mainly as a result of psychiatric disorders such as “Chronic fatigue, depression and dementia” (Tone & Watkins, 2007, p. 134). The texts and images of Ritalin adverts of these early days portrayed the tablet as a prescription drug that defied diagnosis which was mainly administered to patients suffering from psychiatric disorders. It could also be used by patients under other powerful drugs treatment as well as psychotherapy. The images were mainly of middle aged and elderly whites thus displaying the major categories that Ritalin used to treat (Tone & Watkins, 2007, p. 134).

Ritalin was initially marketed in 1955 more directly to geriatric patients as the adverts indicated that the drug was friendly to the geriatric patients; for example, it highlighted that the drug had a gentle action and mild side effects to geriatric patients. However, the adverts of 1960’s diversified the range of patients who were meant to use this drug. For instance, a particular Ritalin advert was found with four men each with a different diagnosis, not necessarily geriatric, ranging from the age of forty to eighty. These four men and women had a sad expression on their faces and though not frightening, they looked lonely and depressed (Tone & Watkins, 2007, p. 134).

Though most Ritalin adverts were dominated by male and female adults, the use of this category of drugs had already been established by 1955 for treating behavioural issues among the minors. Such results were published by Charles Bradley in 1937, whereby they mostly used tranquilizers. Therefore, synthesis of Ritalin came only to save an already existing problem. Adverts in 1960 suggested Ritalin to children with acute behaviour problems and it was meant to improve school performance. For instance, Ritalin would make a kid anxious; lengthen school work attention as well as improving the relationship between the child and the teachers, fellow child and the parent (Tone & Watkins, 2007, p. 134).

Mechanism of Action

MPH works by impacting chemicals in the brain and nerves that are responsible for hyperactivity and impulse control, thus the mechanism of action has been found through research to be higher intensity of arousal of parts of the brain that control impulse and attention (Taylor, 2003, p. 180).

MPH has been found to be quite beneficial to patients suffering from ADD and ADHD. The stimulant in this drug prevents the presynaptic neurons from reabsorbing dopamine and nor epinephrine and also increases their release into the extra neuronal space. This is because research has shown that patients suffering from these ailments have a deficit of these neurotransmitters in their extreurnal space. The availability and constant circulation of the dopamine and nor epinephrine in the brain normalizes the patient’s behaviour. Dopamine in particular triggers of happiness and is naturally produced when a person undergoes a good experience (Pavuluri & Janicak, 2008, p. 93).

Patients under MPH medication show higher striatal perfusion in the frontal lobes because the left frontal lobe is the centre for impulse control. The stimulants duration of action is postulated to be three to five hours whereby the dose is administered twice a day, before breakfast and before lunch. Each administration should contain 5g of the drug. The patient should be closely monitored, and if the situation does not improve, the dose should be increased gradually up to a maximum daily dose of 0.6 mg/kg. This amounts to 10 or 20g each day which can be administered twice or thrice a day, a description which is mainly meant for children with behavioural problems (Taylor, 2003, p. 180).

The dose administered during lunch break may pose a challenge to teachers and administrators since it has a possibility of even causing stigma to the student. Therefore, though the drug is helpful to the students, the medication may be difficult to be administered during school days. However, once a day dose of MPH was approved in 2000, which was encapsulated in an “oral osmotic (OROS) delivery system and its mechanism of agitation was similar to that of thrice-daily administration” (Taylor, 2003, p. 180).

It has been shown that “increased levels of dopamine and norepinephrine in the brain reduce cases of background firing, and rises signal to noise ratios in the target neurons” (Pavuluri & Janicak, 2008, p. 93). MPH therefore increases children attention while reducing chances of being distracted. However, prolonged intake may result to dependence and tolerance due to amines dopaminergic effects.

Some of the benefits of MPH administration include “improved vigilance, impulse control, fine motor co-ordination and reaction time” (Pavuluri & Janicak, 2008, p. 93). Children under MPH medication have also recorded reduction in responding to irrelevant tasks as well as higher levels of persistence. They have also shown reduced chances of aggression, they are less noisy, have less impulsive behaviour, are less likely to be noncompliant and are not likely to be disrupted. Children with past cases of ADD and ADHD haven been later on found to have a better relationship with their peers, teachers and parents. However, the dosage may have some side effects such as lack of appetite, sleeplessness and mood swings such as irritability, crying and anxiety (Pavuluri & Janicak, 2008, p. 93).

Pharmacokinetics

The knowledge of a half life of a drug is quite significant for the purpose of administration. According to Olson (2010), “half life is the amount of time required for the plasma concentration of a drug to decrease by 50% after discontinuance of a drug” (p. 2).

The half life of MPH is usually three to five hours thus the need for multiple doses in a day. The half life peaks between one and a half to two and a half hours whereby the drug is excreted through urine within twelve to twenty four hours after consumption. MPH impact on the behaviour can be observed within thirty to sixty minutes whereby this may peak within the first to the third hour. The effects on behaviour may then subside from the third to the fifth hour. SR effects are observed within the first to the second hour, peaking within the third to the fifth hour, SR effects are postulated to last for eight hours (Pavuluri & Janicak, 2008, p. 93).

Through extensive research, MPH has been found to be a rapidly absorbed drug in its d-isomer form which freely penetrates the CNS, particularly the Striatum. Due to its rapid absorption and immediate release formulation, the medication can portray dramatic effects which may vary depending with the patient. It is therefore advisable to start administering this medication at a low dosage of ten to fifteen milligrams per day and increase the dosage gradually to a maximum level of 60mg per day irrespective of formulation. The gradual administration may involve additional of 15mg weekly until the patients attains the maximum dosage (Wolraich & Doffing, 2004).

Pharmacotherapy

Pharmacotherapy is the science of using drugs to treat diseases. This has been widely applied in MPH since this drug has been useful in treating various types of diseases. MPH has been the most administered psycho stimulant especially for ADD and ADHD. It is a potent CNS stimulant, whose origin has been postulated to be amphetamine. MPH increases stimulation of dopamine and norepiphrine by inhibiting their re-absorption by the presynaptic neurons and also increases their release capacity.

Dopamine belongs to the brain’s mesombolic system and its presence in the brain improves its neurocognitive function. A constant supervision of patients under MPH medication should be ensured since it may have adverse side effects. For instance, during chronic use of MPH, patients have been observed to have cardiac symptoms, nervousness and insomnia (Norden, Reardon & Wen, 2010, p. 150).

A study was carried out involving three patients suffering from brain tumour. MPH administration was administered to them and there was improved neurobehavioral decline. The drug was meant to be an indirect agonist whose main function was to trigger production of catecholamine into the brain that would control attention and memory. Some of the results observed were “improved attention, arousal, initiation speed of task and speed” (Norden, Reardon & Wen, 2010, p. 150).

Elsewhere a study was carried out involving 26 patients suffering gliomas. Despite the ongoing cranial radiation among the patients, neurocognitive deficits portrayed better cognition after administration of 10g and 30g twice a day. Subjective cognitive functioning also became better as well as mood among the patients consuming 30mg. However, it was postulated that cranial radiation could have contributed to the improvement in cognitive function (Norden, Reardon & Wen, 2010, p150).

Another study was carried out that involved chemotherapy. A placebo controlled double blind trial was carried out on a group of women suffering from breast cancer to test for the effects of d-MPH on fatigue and cognitive dysfunction. For compliance purposes, all women were tested for one cycle after which they underwent chemotherapy in intervals of six months. It was observed that there were no differences of either quality of life or classification of cognitive functioning among the randomized women (Norden, Reardon & Wen, 2010, p. 150).

Pharmacotherapy among pregnant women does not have reliable data but it is not advisable to prescribe MPH among them. If the medication has to be administered, it is important to explain both the benefits and the possible side effects of the drug to her and the developing embryo. MPH is also not recommended among breastfeeding women though there is no reliable data. If it has to be administered, it is recommended that breastfeeding should be discontinued. Again, MPH is not recommended among kids below the age of six (Pagliaro & Pagliaro, 2008).

Among children who are six years of age and above, they can be given dosage of 5g to 10g at the initial stages which should be increased gradually till they attains a daily dosage of 60g per day. Daily dosage above this level is not recommended. Administration of the doses should be concentrated during the periods of greatest academic and other kinds of difficulties. The dosage should be administered twice a day and in case no notable improvement is observed, the dosage should be doubled or increased to thrice a day. The first dose should be given in the morning and the second dose in the afternoon. However, afternoon doses are mainly accompanied with insomnia thus may be difficult for schooling kids. If no improvement is observed within a month of medication, the MPH administration should be discontinued (Pagliaro & Pagliaro, 2008).

Interactions with psychotherapy

Patients who may be undergoing MPH treatment or who are intending to do so need to have an interpersonal relationship with the therapist in order to be able to get help when need arises. Therapists require counselling their patients in the process of therapy ad also guide them in to the appropriate conduct during drug administration. For instance, there are various allergies that should not be associated with MPH administration. Also, cases of drug abuse are highly discouraged during MPH consumption. These are some of the issues that necessitate MPH pharmacotherapy interaction with psychotherapy.

Before a doctor administers this drug to a patient, it is important for the patient to tell him any other medication he may be going through in order to avoid fatal interactions of the drug with other drugs. Some of the drugs that are very important to mention may include “warfarin ‘the blood thinner’, clonidine, dobutamine, epinephrine, or isoproterenol” (Multum, 2010, p. 1) since they may have severe side effects. Also it is important to mention to the doctor before MPH is administered is that any medicine for treating blood pressure, diet pills, and other kinds of stimulants, seizure medicine, and any antidepressant (Multum, 2010).

Conclusion

Since MPH was synthesised in the 1940’s, it has been extensively used in the medical field as the major stimulant. It is the most commonly administered stimulant drug especially among schooling children suffering from ADD and ADHD. Before 1954, many patients suffering from these disorders mainly used tranquilizers after which it replaced most of them due to its extensive usage. MPH is mainly consumed twice a day, before breakfast and at noon.

It should be administered initially with lesser doses of about 5g per day since it may have dramatic impact on the patient. The dosage is gradually increased up to the level of 60g daily taking into consideration how the person taking it responds to it. It should not be taken beyond six in the evening since it is mainly, meant to sustain attention. If patients do not show improvement, the dosage should be doubled probably on weekly basis but should not go beyond 6og per day. If no improvement is recorded in a month, the medication should be discontinued and further assistance sought form the therapist.

Various studies have been carried out among people from different age groups. Among the children, the drug has recorded reduction in responding to irrelevant tasks as well as higher levels of persistence. They have also shown reduced chances of aggression, they are less noisy, have less impulsive behaviour, are less likely to be noncompliant and are not likely to be disrupted. Children with past cases of ADD and ADHD are later on found to have a better relationship with their peers, teachers and parents. However, the dosage may have some side effects such as lack of appetite, sleeplessness and mood swings such as irritability, crying and anxiety. It has also recorded trends of improvement in cognitive functioning among adults with brain tumours or suffering from other ADHD related ailments.

MPH does not lack a few side effects which calls for close supervision during its administration since they may at times turn very severe or fatal. Some of the common side effects include, fast, pounding or uneven heartbeats, unconsciousness, fatigue, nervousness, sleeplessness, may trigger chances of alcoholism, fever, sore throat, headache, hypertension among others. However, if taken alongside interactive psychotherapy, it is possible to manage some of the side effects.

MPH is rapidly absorbed in to the body and it does last for twelve to twenty four hours in the body before it is excreted in to the urine. It has a half life of two to three hours which may reach peak in the third hour. Chronic or prolonged use of this drug may result in to dependence or tolerance.

References

Multum, C. (2010). Concerta. Drugs. Web.

Norden, A., Reardon, D. & Wen, P. (2010). Primary Central Nervous System Tumors: Pathogenesis and Therapy. New York, NY: Springer.

Olson, J. (2010). Clinical Pharmacology Made Ridiculously Simple. New York, NY: Medmaster.

Pagliaro, L. & Pagliaro, A. (2008). Psychologists’ psychotropic drug reference. New York, NY: Psychology press.

Pavuluri, M. & Janicak, P. (2008). Handbook of Psychoparmacotherapy: A Lifespan approach. New York, NY: Lpicott Williams & Wilkins.

Rxlist, (2011) Concerta Drug Description.Rx List. Web.

Taylor, R. (2003). Family Medicine, Principles and Practice. New York, NY: Springer.

Tone, A. & Watkins, E. (2007). Medicating Modern America: Prescription Drugs in History. New York, NY: New York University Press.

Wolraich, M. A. & Doffing, M.L. (2004). Pharmacokinetic considerations in the treatment of attention-deficit hyperactivity disorder with methylphenidate. National Centre for Biotechnology Information (NCBI). Web.

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