3. Psychomotor Stimulants Flashcards
Attention Deficit Hyperactivity Disorder (ADHD)
Other names: ____ Syndrome
Attention Deficit Disorder (ADD)
Minimal Brain Dysfunction with Hyperactivity
Signs / Symptoms
- increased ____ activity
- impaired ____
- ____ attention span
- easy ____
- ____ behavior
- learning ____
____ does not always occur in ADHD.
hyperkinetic
motor coordination short distractibility impulsive disability
hyperactivity
ADHD
Etiology
Unknown. May be related to deficiency in brain ____.
ADHD estimated to affect 5% of children & 2.5% of US adults.
Association between ADHD and earlier-onset substance abuse; ____ not proven.
catecholamines
causation
ADHD
Drug Therapy
Appears to be successful in approximately ____% of cases.
By increasing the ability to concentrate and perform a task, selected drugs seem to ____ the patient during work projects.
2011: >52 million Rxs ADHD meds / ____% inc from 2010.
75
calm
10
ADHD
CNS Stimulants
Caffeine: ____
Amphetamines = ____ > pemoline
Other:
Antidepressants:
– ____:
imipramine & desipramine have some efficacy but are toxic
– ____ Inhibitors:
efficacy = amphetamine & methylphenidate but are too toxic
Barbiturates: ____ (+ paradoxical ____)
Clonidine: useful in ____ cases
ineffective
methylphenidate
tricyclic
MAO
ineffective
excitation
limited
ADHD
1. Caffeine Does not appear to be \_\_\_\_ in ADHD. At doses > \_\_\_\_ mg / day, 'caffeinism' may occur with symptoms such as: \_\_\_\_ Headache \_\_\_\_ Increased muscle tension
Caution in pts with diabetes: may cause unacceptable ____.
effective
500
anxiety
insomnia
hyperglycemia
ADHD
- Amphetamines
Amphetamine; methamphetamine (DESOXYN).
Powerful ____ stimulants.
____ mg, p.o., will produce a significant increase in CNS activity in the non-tolerant person.
Tmax of dextroamphetamine approximately ____ hrs.
Mechanisms of action: a. Major: \_\_\_\_ stimulation of CNS via: 1) promote release of \_\_\_\_ from pre-synaptic storage sites 2) inhibit re-uptake of released \_\_\_\_ at pre-synaptic membrane
b. Minor
1) ____ stimulation of post-synaptic adrenergic receptors
2) inhibition of ____
CNS 5-10 3.5 indirect catecholamines re-uptake
direct
MAO
Amphetamines
Uses \_\_\_\_: short-term (only 4-8 weeks) \_\_\_\_ Ø excessive sleepiness Ø sleep 'attacks' Ø sleep paralysis \_\_\_\_
weight loss
narcolepsy
ADHD
Amphetamines
ADRS
Acute \_\_\_\_ Elevated blood pressure \_\_\_\_ Anorexia
____
Gilles de la Tourettes Syndrome (involuntary tics): motor: ____, body, limbs
verbal: ____, phrases (may be obscene)
appears to be related to excessive central ____ activity
Chronic
Same as acute plus:
____ weight gain: inhibits growth of children Psychological dependence
Development of significant ____ & physical dependence (addicts may use from 1-2 grams per day!)
Toxic ____
tachycardia insomnia tachyphylaxis head words DA
decreased
tolerance
psychosis
Amphetamines
ADDERALL
____ formulation. Combines neutral sulfate salts of ____ and amphetamine, with the dextro isomer of ____ and d,l-amphetamine aspartate monohydrate.
immediate release
dextroamphetamine
amphetamine saccharate
Amphetamines
ADDERALL XR
____ daily extended-release, single-entity amphetamine product [same as Adderall regular tablets].
Adderall XR capsule contains ____ types of drug-containing beads designed to give a ____-pulsed delivery of amphetamines, which prolongs release of amphetamine from Adderall XR compared to the conventional ADDERALL ® immediate-release) tablet formulation.
once
two
double
Amphetamines
ADDERALL XR
• There are adults with ADHD. Does that mean chronic therapy? ____.
• Amphetamines are not ripping apart tissues. The more that a drug acts like a ____ product,
the less ripping apart. Alcohol degenerates cardiac muscle and skeletal muscle and brain tissue.
- Amphetamines, on the other hand does not have too much ____ damage - Someone could be on these for a ____.
yes
natural
pathologic
lifetime
Lisdexamfetamine dimesylate (Vyvanse®) CII
Prodrug of ____.
Does not bind to ____ reuptake sites.
Converted to dextroamphetamine and l-lysine primarily in ____
due to the hydrolytic activity of ____. Significant hydrolysis
even at low ____ levels (33% of normal).
T1⁄2 < ____ hr
ADHD
Moderate to Severe Binge Eating Disorder (BED)
Safety and effectiveness for Tx of ____ have not been
established.
NOT indicated for ____.
Use of other sympathomimetic drugs for weight loss has been
associated with serious ____ adverse events.
Prior to treatment, assess for presence of ____ disease
Severe renal impairment: Maximum dose is ____ mg/day
End stage renal disease (ESRD):
Maximum dose is ____ mg/day
dextroamphetamine NE and DA blood RBCs hematocrit
1
obesity
weight loss
cardiac
50
30
ADHD Initial dose: \_\_\_\_ mg every morning Titration schedule: \_\_\_\_ mg weekly Recommended dose: \_\_\_\_ mg per day Maximum dose: \_\_\_\_ mg per day
30
10 or 20
30 to 70
70
BED
Initial dose: ____ mg every morning
Titration schedule: ____ mg weekly
Recommended dose: ____ mg per day
Maximum dose: ____ mg per day
30
20
50 to 70
70
Warnings/Precautions
Serious Cardiovascular Reactions: ____ in children and adolescents with serious heart problems, as well as sudden death, stroke, and myocardial infarction in adults reported. Avoid use in patients with known structural cardiac ____,
cardiomyopathy, serious heart ____, or coronary artery
disease.
BP and Heart Rate Increases: Monitor ____ and pulse.
Consider benefits and risks before use in patients for whom ____ increases may be problematic
sudden death
abnormalities
arrhythmia
blood pressure
blood pressure
Psychiatric: May cause ____ or manic symptoms in patients with no prior history, or exacerbation of symptoms in pts with pre-existing psychosis. Evaluate for ____ prior to
stimulant use
Suppression of Growth: Monitor height and weight in pediatric pts during Tx.
Peripheral Vasculopathy, including Raynaud’s phenomenon:
Stimulants assoc with ____, including Raynaud’s phenomenon. Careful observation for ____ changes
necessary during Tx with stimulants
psychotic
bipolar disorder
peripheral vasculopathy
digital
Lisdexamfetamine dimesylate (Vyvanse)
ADRs:
Incidence ≥5% and at rate at least 2x placebo
\_\_\_\_
\_\_\_\_
dec weight
--\_\_\_\_
--dizziness
--dry \_\_\_\_
--irritability
--\_\_\_\_
--N/ V
upper abdominal pain
anorexia anxiety diarrhea mouth insomnia
Lisdexamfetamine dimesylate (Vyvanse)
Acidifying agents: ____ amphetamine blood levels
Alkalinizing agents: ____ amphetamine blood levels.
- You can look at the ____ as one of the ways of helping. Because amphetamines are a weak base, the docs will decide to acidify the urine to cause the amphetamine to be more ionized and more ____ soluble, then will get eliminated.
- Something you would never do in the ER is to alkalinize the urine because again this is a weak base, so it would ____ amphetamine blood levels. As amphetamine comes into the renal system, it is not ionized in an alkaline environment, and it is reabsorbed.
dec
inc
urine
water
inc
Adzenys XR-ODT (Amphetamine Extended-Release Orally disintegrating Tablet) for Tx of ADHD in Pts 6 years and older
First and Only FDA Approved \_\_\_\_ Orally Disintegrating Tablet (ODT) for Tx of ADHD
Bioequivalent to a previously approved mixed ____ extended-release capsule (Adderall XR®1), one of the most commonly prescribed medications for the treatment of ADHD.
Adzenys XR-ODT contains amphetamine loaded onto a mixture of ____ release and ____-coated, delayed-release resin particles; designed to disintegrate in ____.
____-protected; not generic of amphet. mixed salts XR capsules.
Available in six dosage strengths, equivalent to the Adderall XR® dosage strengths, thus allowing healthcare providers to
____ the dose.
extended-release amphetamine salts immediate polymer mouth patent individualize
Adzenys XR-ODTTM (Amphetamine Extended-Release Orally Disintegrating Tablet) for Tx of ADHD in Pts 6 Years and Older
Potential for Overdose Due to Medication Errors:
Med errors, including ____ and dispensing errors with
other amphetamine products could occur, leading to possible ____.
Do not substitute for other amphetamine products on a ____ basis, because of different amphetamine base
____ and differing ____ profiles
substitution
OD
milligram-per-milligram
compositions
pharmacokinetics
Adzenys XR-ODTTM (Amphetamine Extended-Release Orally Disintegrating Tablet) for Tx of ADHD in Pts 6 Years and Older
WARNING: ABUSE AND DEPENDENCE
CNS stimulants, including Adzenys XR-ODT, other amphetamine-
containing products, and methylphenidate, have a high potential
for ____. Assess the risk of abuse prior to
prescribing and monitor for signs of abuse and dependence while
on therapy.
abuse and dependence
Adzenys XR-ODTTM (Amphetamine Extended-Release Orally Disintegrating Tablet) for Tx of ADHD in Pts 6 Years and Older
Contraindications: Pts should not take Adzenys XR-ODT if they are:
• ____ to amphetamine or other ingredients of Adzenys XR-ODT. ____ and anaphylactic reactions have been reported in patients treated with other amphetamine products.
• Taking ____, or have taken an MAOI within the past 14 days. ____ crisis can occur.
hypersensitive
angioedema
monoamine oxidase inhibitors
hypertensive
Adzenys XR-ODTTM (Amphetamine Extended-Release Orally Disintegrating Tablet) for Tx of ADHD in Pts 6 Years and Older
READ ME
Warnings and precautions
- Serious ____ Reactions: Sudden death has been reported in association with CNS stimulant treatment at recommended doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infraction have been reported. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Adzenys XR-ODT treatment.
- ____ and Heart Rate Increases: CNS stimulants can cause an increase in blood pressure (mean increase about 2-4 mm Hg) and heart rate (mean increase about 3-6 bpm). Monitor all patients for potential tachycardia and hypertension.
- ____ Adverse Reactions: Prior to treatment assess for the presence of bipolar disorder. CNS stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychosis.
- Long-Term Suppression of ____: CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor weight and height in pediatric patients treated with Adzenys XR-ODT. Treatment may need to be interrupted in children not growing as expected.
- ____, including Raynaud’s Phenomenon: CNS Stimulants, including ADZENYS XR-ODT, are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation may be required, including referral.
- ____: Use only if the potential benefit justifies the potential risk to the fetus. Based on animal data, Adzenys XR-ODT may cause fetal harm. Breastfeeding is not recommended during treatment with Adzenys XR-ODT.
cardiovascular blood pressure psychiatric growth peripheral vasculopathy pregnancy and lactation
- Methylphenidate (RITALIN; RITALIN SR)
Similar to amphetamines but less ____ stimulation & less ____ activation.
Major drug of ____
Uses
ADHD: regarded by many physicians as ____
____ mg/kg (low dose) = improved behavior & learning
• not for children < ____ years old
• > ____ mg not recommended for children 6 years & older
ADRs
More likely to occur at ____ mg/kg
Similar actions as amphetamines but less intense Less inhibitory effect on growth
Motor ____
Additional Uses
Depression
Ø in ____ pts as alternate to antidepressants
Ø in ____ pts
Antagonism of ____-induced sedation in cancer pts
CNS
CV
abuse
D.O.C
0.3
6
60
1.0
tics
geriatric
stroke
opioid
CONCERTA®
Extended-release tablet for ____-a-day ____ administration; contains 18, 36 or 54 mg of ____ HCl.
DAYTRANA
____.
10 mg during 9 hrs of placement on ____ as recommended; avoid ____).
Effects continue for up to ____ hours after removal.
once
oral
methylphenidate
transdermal
hip
waistline
2-3
Dexmethylphenidate (FOCALIN®) ____; more ____ in treating ADHD
Focalin XR Strength
FDA has approved Focalin XR (dexmethylphenidate extended- release capsules for addition of a 15 mg strength. Indicated for Tx of ADHD in pts ____ years of age and older.
d-isomer
potent
6
Extended Release Liquid ADHD Medication
Quillivant – Methylphenidate
Researchers determined efficacy of Quillivant XR by thru
____, ____, ____-controlled study of 45 children with ADHD.
Children received an initial ____mg dose once daily in the morning.
Dosage then titrated weekly until optimal dose or a maximum dose of ____mg per day was reached.
Then a two-week double-blind study performed using a crossover design: children alternated between med or placebo.
At end of each week, trained observers evaluated the attention and behavior of the patients in a laboratory classroom using an
established behavioral rating scale.
Quillivant XR significantly improved ____ symptoms compared to placebo at the primary endpoint of four hours post-dose.
Secondary analysis, showed significant improvement at every time point measured, from 45 minutes to 12 hours after dosing.
randomized double-blind placebo 20 60 ADHD
- Clonidine (CATAPRES)
____ adrenergic agonist at pre-synaptic membrane:
Ø decreased release of ____ NE from locus ceruleus
Ø effect oppostite that which appears necessary for successful pharmacological management of ____.
Use: Alone or with methylphenidate when: Ø prominence of \_\_\_\_ symptoms Ø family history of \_\_\_\_ disorders Ø presence of severe \_\_\_\_ disorder
ADRs: ____; Bradycardia; ____
alpha-2
catecholamines
ADD
aggressive
tic
conduct
sedation
hypotension
- Antidepressants
Limited to pts unresponsive to stimulant therapy
Include: ____ (TOFRANIL; Desipramine (NORPRAMIN)
Many ADRs
Ø ____
Ø some are potentially fatal
• e.g., cardiac arrhythmias (prolonged ____ interval)
• at least three children have died suddenly (no OD)
imipramine
anticholinergic
QT
Antidepressants
Atomoxetine (STRATTERA)
Capsule; can be taken once or twice a day..
FDA approved it as safe and effective for treatment of ____ in children, adolescents, and adults.
Selective \_\_\_\_ reuptake inhibitor. Only FDA-approved ADHD medication clinically proven effective for \_\_\_\_. First non-\_\_\_\_ medication approved for the treatment of ADHD in children, adolescents, and adults. Non-controlled prescription medication: can \_\_\_\_ by phone. Can write Rx for > than \_\_\_\_ month.
ADHD norepinephrine adults stimulant refill one
- (Modafinil)PROVIGIL [C-IV]
FDA approval for narcolepsy, a disabling disorder characterized by excessive daytime ____.
Physicians have been prescribing it for other conditions; estimation is that 80 percent of Provigil Rxs are for “____” treatment of sleepiness and fatigue from other illnesses, including ____, sleep apnea, Parkinson’s disease, ____ syndrome, and multiple sclerosis.
Mechanism unknown. May facilitate ____ activity and reduce release of ____. Blocks ____ reuptake. Similar to other psychostimulant drugs as cocaine. Has been shown to produce ____ symptoms upon discontinuation.
sleepiness off-label depression chronic-fatigue glutamate GABA DA withdrawal
- (Modafinil)PROVIGIL [C-IV] (continued)
Limited ____ liability; less likely to produce those central and
peripheral adverse effects caused by other psychostimulants.
American Academy of Sleep Medicine classifies shift work sleep disorder as a ____ sleep disorder; characterized by excessive sleepiness during work shifts, mainly at night, when people would normally be sleeping.
Shift workers complain of ____ at work, ____ during the day. Studies show that routine sleep loss can accelerate risk of serious health problems, including ____ cardiac abnormalities.
Cephalon conducted a study of several hundred people with shift work sleep disorder; those who took Provigil stayed awake on the job more than those on placebo. In two other studies involving 484 people suffering from sleep apnea, Provigil helped subjects stay awake, compared with placebo, according to the company.
FDA Peripheral and Central Nervous System Drugs Advisory Comm. recommended the label for Provigil (modafinil) [C-IV] be expanded. This recommendation was based on clinical studies demonstrating safety and effectiveness of Provigil in patients with excessive sleepiness associated with ____, obstructive sleep apnea, and ____ sleep disorder.
abuse circadian rhythm sleepiness insomnia GI
narcolepsy
shift work
Armodafinil (NUVIGIL) ãIV
–____-promoting agent for p.o. admin
____ of modafinil (mixture of R- & S-enantiomers)
Indication: pts having excessive ____ associated with;
obstructive sleep apnea/hypopnea syndrome
____
shift work sleep disorder
Armodafinil and modafinil wake-promoting actions » ____ agents including amphetamine and methylphenidate
… but ____ profile not identical to these drugs.
wakefulness R-enantiomer sleepiness narcolepsy sympathomimetic pharmacologic
Armodafinil (Nuvigil)
Modafinil produces ____ and euphoric effects, alterations
in mood, perception, thinking, and feelings typical of other CNS
stimulants in humans.
Precise mechanism of armodafinil & modafinil in this action is ____
At ____ relevant concentrations, armodafinil does
not bind to or inhibit several receptors and enzymes potentially relevant for sleep/wake regulation, including those for ____, DA, adenosine, galanin, melatonin, ____, orexin-1, orphanin,
PACAP or benzodiazepines, or transporters for GABA, 5HT, NE, and choline or phosphodiesterase VI, COMT, GABA transaminase, and tyrosine hydroxylase.
psychoactive unknown pharmacologically 5HT melanocortin
Armodafinil
Modafinil does not inhibit ____ or ____.
Wakefulness can be attenuated by the ____-adrenergic receptor antagonist, prazosin;
Armodafinil – not direct or indirect-acting ____ receptor agonist.
However, in vitro, both armodafinil and modafinil bind to ____ transporter and dec ____ uptake. For modafinil, this activity has been associated in vivo with increased extracellular ____ levels in some brain regions of animals.
In genetically engineered mice lacking the dopamine transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was ____-dependent.
However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not ____ by the dopamine receptor
antagonist haloperidol in rats.
In addition, alpha-methyl-p-tyrosine, a dopamine synthesis
inhibitor, blocks the action of ____, but does not block ____ activity induced by modafinil.
MAO-B phosphodiesterases (II-IV) alpha1 dopamine DA DA DA
DAT
antagonized
amphetamine
locomotor
