ATOMOXETINE &METHYLPHENIDATE

- DR DEEPIKA SINGH, RESIDENT, DEPT OF PSYCHIATRY, GSMC & KEMH

DRUG TREATMENT:• STIMULANT DRUGS- METHYLPHENIDATE- DEXTROAMPHETAMINES

• NONSTIMULANT DRUGS- ATOMOXETINE HCL- BUPROPION- VENLAFAXINE- CLONIDINE, GUANAFACINE

HISTORY

-Methylphenidate was first synthesized in 1944, and was identified as a stimulant in 1954.

-Methylphenidate was synthesized by Ciba (now Novartis) chemist Leandro Panizzon.

-Beginning in the 1960s, it was used to treat children with ADHD or ADD

Methylphenidate (Ritalin, MPH, MPD) is a

psychostimulant drug approved for treatment of --ADHD

-Narcolepsy -Treatment-resistant depression

Molecular formula: C14-H19-N-O2

Other systematic names: 2-Piperidine acetic acid, alpha-phenyl, methyl ester

BRANDS & AVAILABLE FORMS• The dosage forms of methylphenidate are tablets, capsules, patches,

and liquid. • A formulation by the Novartis trademark name Ritalin, is an

immediate-release racemic mixture, although a variety of formulations and generic brand names exist.

• Generic brand names include Ritalina, Rilatine, Attenta, Metadate, Methylin, and Rubifen.

• sustained release tablets or capsules Concerta, Metadate CD, Methylin ER, Ritalin LA, and Ritalin-SR

• Focalin is a preparation containing only dextro-methylphenidate• Transdermal patch (under the brand name Daytrana)

MECHANISM OF ACTION

• ENHANCEMENT OF

DOPAMINE

1) Dorsolateral pre frontal cortex

2) Basal ganglia3) Medial prefrontal cortex

& Hypothalamus

SIDE EFFECTS• COMMONLY SEEN:-Insomnia-Headache-Dizziness-Tremor-Anorexia-Abdominal pain-Weight loss

• LIFE THREATENING SIDE EFFECTS:- Psychotic episodes- Seizures- CVS adverse effects

• PHARMACOKINETICS:Half lifeAdults- 3.5 hrsChildren- 2.5 hrs

DOSAGE• ADHD- Upto 2mg/kg/day

in children > 6yrs agemax dose 60mg/day

- Adults : 20-30mg/day max dose 40-60mg/day

• NARCOLEPSY- 20 to 60 mg/day

in 2-3 divided doses

• IMMEDIATE RELEASE TABLET

2 to 4 hrs duration of action

• EXTENDED RELEASE TABLET(RITALIN SR, METADATE ER)4 to 6 hrs duration of action

• NEWER SUSTAINED RELEASE TABLET-CONCERTA12 hrs duration of action-RITALIN LA & METADATE CD 8 hrs duration of action

CONCERTA

ABUSE POTENTIAL

- Schedule II drug- Methylphenidate has high potential for abuse due to its pharmacological similarity to cocaine and amphetamines- Methylphenidate, like other stimulants, increases dopamine levels in the brain, but at therapeutic doses this increase is slow, and thus euphoria does not typically occur except in rare instances.- The abuse potential is increased when methylphenidate is crushed and insufflated (snorted), or when it is injected, producing effects somewhat similar to cocaine.

DRUG INTERACTIONS

1) Methylphenidate use within 14 days of MAO inhibitors is not advised

2) It could inhibit antipsychotic drugs actions3) No dose adjustments in hepatic & renal

impairment, used with caution in cardiac impairment

ATOMOXETINE

ATOMOXETINE It is a selective norepinephrine reuptake inhibitor approved for the treatment of attention-deficit hyperactivity disorder (ADHD).

Atomoxetine was originally known as "tomoxetine". However, the U.S. Food and Drug Administration (FDA) requested the name be changed because of the similarity of "tomoxetine" to "tamoxifen" could lead to dispensing errors at pharmacies.

• Atomoxetine is designated chemically as N-methyl-3-phenyl-3-propylamine

hydrochloride

BRANDS:- Strattera- Attentrol- Axepta

MECHANISM OF ACTION

• Despite its name selective norepinephrine reuptake inhibitor , it enhances both Dopamine & Norepinephrine in frontal cortex

• Atomoxetine may be preferred over amphetamine-based stimulants in patients with :

• psychiatric disorders, • those who cannot tolerate stimulants,• and those with a substance misuse recurring

history.

SIDE EFFECTS

• Commonly seen:-decreased appetite-increase HR & BP-Insomnia, dizziness, anxiety, agitation ,

aggression, irritability, sweating-Dry mouth , nausea , vomiting, dyspepsia,

abdominal pain, -Urinary hesitency & retention-Sexual dysfunctions

• DANGEROUS SIDE EFFECTS:- Increase HR & BP- Liver damage- Induction of mania- Suicidal ideation

• PHARMACOKINETICS:Hepatic Metabolism by CYP450 2D6Half life 5 hrsExcretion : mainly urine Time to peak , plasma: 1-2 hrs

DOSAGE

• 0.5 to 1.2 mg/kg/dayIn children upto 70kg

Max dose 1.4mg/kg/day or 100mg/day whichever less

-40 to 100 mg/day in adults

ABUSE POTENTIAL

• Lack of enhancing dopamine activity in limbic area theoretically explains atomoxetine’s lack of abuse potential.

DRUG INTERACTIONS

• Drugs inhibiting CYP 450 2D6 increases plasma concentration of atomoxetine

• Atomoxetine not to be used with or within 14 days of MAOIs use.

• No dose adjustment in renal impairment• Dose adjustment required in hepatic

impairment• Caution in cardiac impairment.

THANKYOU…

REFERENCES

1] Kaplan & Sadock’s ComprehensiveTextbook Of Psychiatry2] Stephen Stahl's Essential Psychopharmacology3] Stephen Stahl’s Prescribers guide4] The Maudsley’s PrescribingGuidelines

QUESTIONS