Drugs - ADHD (Martin) Flashcards
name 4 main stimulant drugs for ADHD
methylphenidate (Ritalin)
Dexmethylphenidate
Dextroamphetamine (Vyvanse)
Amphetamine mixed salts (adderall)
all classified as controlled substances (Schedule II) Controlled substances (Schedules II-V) cannot be sold without a prescription.
- High potential for abuse.
- Has a currently accepted medical use in the United States.
- Abuse of substance may lead to severe psychological or physical dependence.
non stimulant drug for ADHD
atomoxetine (strattera)
alpha 2 agonists used for ADHD
clonidine
guanfacine
diagnosis of ADHD is made before what age
before age 12
• Some impairment from symptoms is present in two or more settings, e.g., school or work and home and babysitter’s house and with friends and etc. Clear evidence of clinically significant impairment in social, academic, or occupational functioning.
first line treatment for ADHD
methylphenidate
followed by dextroamphetamine and amphetamine mixed salts
when is atomoxetine a good option
Atomoxetine is used if the family objects to the use of a controlled substance stimulant, if weight loss is a problem, or for patients with mood, anxiety, tic or substance abuse disorders.
what are people with untreated ADHD at risk for
- Several studies have shown that patients with untreated ADHD have twice the risk for substance abuse, with earlier onset, and less likelihood to recover as an adult, than ADHD patients who have received treatment.
- Effective management of ADHD significantly decreases the risk of substance abuse.
NET?
o Responsible for clearing released NE from synaptic space.
o Can also transport dopamine; affinity for dopamine > NE.
o NET blocked by cocaine, atomoxetine, SNRIs (venlafaxine, desvenlafaxine, duloxetine) and TCAs.
o Amphetamine is a substrate for NET, blocks normal NE reuptake, and reverses the transport so that NE is released (see B above).
DAT
dopamine transporter
o Localized primarily in the brain at dopaminergic synapses on presynaptic sites and also in abundance along the neurons away from the synapse.
o Also has weak affinity for NE.
o DAT is blocked by methylphenidate, cocaine and the neurotoxin, MPTP.
o Amphetamines block uptake and reverses transport, higher doses required for effects on DA compared to NE (see B above).
SERT
serotonin transporter
o Located in periphery and brain along extrasynaptic axonal membranes.
o SERT is blocked by SSRIs, SNRIs, TCAs and by high concentrations of amphetamines.
o Methamphetamine and halogenated amphetamines, fenfluramine, dexfenfluramine, may also be neurotoxic to 5-HT neurons.
use of short acting methylphenidate (ritalin)
onset 30 min
duration 3-5 hrs
IR-MPH tablets are sometimes used concurrently with long-duration forms either to provide a boost early in the morning, or to smooth withdrawal in the late afternoon.
use of long acting methylphenidate
name three important ones
Despite the effectiveness of IR-MPH, its 3-5 hour duration of action usually requires mid-day dosing in school, which children may find disruptive or stigmatizing. The short duration of action also requires administration by non-family adults when children participate in after-school programs. Long-duration MPH preparations with once-daily dosing have therefore become the mainstay of clinical practice.
Ritalin LA- beaded double pulse
Concerta- osmotic release
daytrana - transdermal
Ritalin LA
beaded double pulse
long acting
Beaded MPH products use an extended- release formulation with a bi-modal release mechanism. With Ritalin LA and Focalin XR, half the dose is in immediate-release beads and half in enteric-coated, delayed-release beads. Metadate CD contains 30% immediate-release beads and 70% delayed-release beads. In young children who have difficulty swallowing pills, the capsules can be opened and the beads sprinkled into a small amount of cold applesauce or vanilla ice cream to disguise the bitter taste.
Concerta
long acting methylphenidate
The Concerta tablet uses an osmotic delivery system to extend the duration of action of MPH to up to 12 hours. The tablet is coated with IR-MPH for immediate action. The rest of the dose is delivered by an osmotic pump that gradually releases the drug over a 10-hour period, producing slightly ascending MPH serum concentrations. Taken once daily, serum concentrations are similar to those produced by taking IR-MPH three times daily, but with less variation. The tablets themselves are excreted intact in the stool.
Daytrana
transdermal long acting methylphenidate
After application of the transdermal patch, there may be a 2-hour delay in its onset of action that can be a disadvantage when getting children ready for school. MPH is steadily absorbed and reaches peak concentrations in serum after 7-9 hours. Chronic dosing with the patch results in higher peak MPH levels than with equivalent doses of OROS-MPH. The duration of MPH action for a 9-hour wear period is about 11.5 hours. One advantage of the patch formulation is that it can be removed early in patients who have a problem with insomnia.
ADR’s of daytrana
, but adverse effects such as anorexia, insomnia, and tics have occurred more frequently with the patch formulation. Mild skin reactions are common.
what types of substances increase or decrease absorption, or increase or decrease excretion in the urine of amphetamines
Taking the drug with ascorbic acid or fruit juice tends to decrease absorption of amphetamine, while alkalinizing agents such as sodium bicarbonate tend to increase absorption. Acidification of the urine increases amphetamine excretion.
Dextroamphetamine
The onset of action of dextroamphetamine occurs within one hour of ingestion, and its duration of action is up to 5 hours, somewhat longer than that of MPH. Twice-daily administration is needed to extend the treatment throughout the school day, and children may dislike taking the second dose in school.
Dextroamphetamine has been as effective as MPH in decreasing overactivity, impulsivity and inattention in children with ADHD. Some children unresponsive to MPH may respond to dextroamphetamine, and vice versa. Absorption of dextroamphetamine is rapid; plasma concentrations reach a peak 3 hours
Adderall
amphetamine mixed salt
Adderall XR is a double-pulse capsule formulation that contains both immediate-release and extended release beads. There is no evidence that these mixed amphetamine salts offer any advantage over MPH or dextroamphetamine, but some patients respond to one and not to another.
Vyvanse
lisdexamfetamin dimesylate- short acting dextroamphetamine
is a prodrug in which d-amphetamine is covalently bonded to L-lysine.
Lisdexamfetamine dimesylate has a longer duration of action than that of other amphetamine preparations, which may be an advantage for use in working adults. Its efficacy appears to be similar to that of other amphetamines.
what are some common adverse effects of stimulants
- methylphenidate
- dexmethylphenidate
- amphetamines
- Common side effects: delayed sleep onset, headache, decreased appetite and weight loss.
- Some older children say that stimulants make them feel less spontaneous and less comfortable in their social interactions. Drug holidays during weekends and vacations may be helpful, particularly in making up for weight loss and slow growth.
what are some infrequent adverse effects of stimulants
emotional lability and either new onset or an increase in the frequency of tics. Tactile and visual hallucinations can occur. Stimulants can slow growth and possibly lower the convulsive threshold. They should be used with great care in patients with a history of mania, psychosis, drug dependence or alcoholism
CI in kids with heart defects
Patients with pre-existing heart disease should be referred to a cardiologist before starting stimulant treatment.
what are some adverse effects that are the most common to cause discontinuation of treatment
• The most common adverse events leading to discontinuation of treatment with stimulants have been motor or vocal tics, anorexia, insomnia and tachycardia.
contraindications for using stimulants for ADHD
• Contraindications – Clinical conditions that can be exacerbated by stimulant treatment include psychosis, mania, Tourette syndrome and closed-angle glaucoma.
atomoxetine
- A selective norepinephrine reuptake inhibitor, atomoxetine (Strattera) was the first drug to be approved by the FDA to treat ADHD in both children and adults. It is neither a controlled substance nor a stimulant.
- Atomoxetine is rapidly absorbed, with peak serum concentrations occurring within 1 hour without food and in
how does atomoxetine compare in efficacy to stimulants
• Atomoxetine is less effective than the stimulants in reducing the symptoms of ADHD. Its greatest value is for patients who have not responded to or cannot tolerate stimulants, particularly children with low weight and short stature and those who refuse to be treated with a controlled substance.
Atomoxetine ADR’s
• Adverse Effects – Somnolence, nausea and vomiting have occurred in children starting atomoxetine, particularly when the dose is increased from starting to maximum levels within a few days. Decreased appetite can occur, but is much less of a problem than with stimulants. The FDA has required that atomoxetine labeling include a black box warning about a possible association with suicidality.
Clonidine and Guanfacine
- Stimulate α2-adrenergic receptors, especially centrally.
- Decrease central sympathetic output.
- Clinically useful for treating tics and hypertension.
- Also used in children to manage sleep problems, aggression, and self-injury behavior.
- Clinical trials show clonidine and guanfacine to have moderate efficacy for treating ADHD; less efficacious than stimulants; can be used as an adjunct to another ADHD drug.
- Appears to improve symptoms of hyperactivity and impulsivity, but not distractibility
- Must be tapered down slowly when discontinuing so as to avoid sudden hypertensive crisis.
use of bupropion in ADHD
- Shown effective for treating ADHD is small trials but is not FDA approved.
- A NE reuptake inhibitor used as an antidepressant
- Contraindicated in patients with current seizure disorder because it lowers the seizure threshold.
TCA’s used in ADHD
• Imipramine, desipramine, nortriptyline
- Some efficacy for relieving the symptoms of ADHD, but not FDA-approved, and not first-line treatment.
- May be helpful for treatment of hyperactivity and impulsivity in patients that have been treatment-resistant to more than two trials with stimulants, as well as, non-stimulant medications.
- Less effective for treatment of distractibility than stimulants.
Modafinil (Provigil)
NE reuptake inhibitor
•
Modafinil is a non-stimulant drug with mild cardiovascular effects used for treatment of narcolepsy; it has also been used off-label for treatment of ADHD.
• Hallucinations and Stevens-Johnson syndrome have been associated with its use, and the manufacturer has withdrawn its application for FDA approval for use in patients with ADHD.
