ADHD PHARMACOLOGY University of Hawaii Hilo Pre -Nursing Program NURS - PowerPoint PPT Presentation

ADHD PHARMACOLOGY University of Hawai‘i Hilo Pre -Nursing Program NURS 203 – General Pharmacology Danita Narciso Pharm D 1

 Understand what happens in “filter & gain” under normal circumstances and how that translates to ADHD  Understand the pharmacology behind the medications used to treat ADHA  Understand the general pharmacologic profiles of the classes of medications used to treat ADHA and the individual characteristics of medications within those classes that give them a niche in therapy LEARNING OBJECTIVES 2

 Definition of ADHD  Under normal circumstances (filter and gain)  Risk factors for ADHD  Types of ADHD and diagnosis  Medications used to treat ADHD OVERVIEW 3

 A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development WHAT IS ADHD? 4

- +/- - + ADHD + Pharmacology 5

- +/- - + ADHD + Pharmacology 6

D1 7 HCN (Funny) Dopamine Potassium Channel

D1 8 HCN (Funny) Dopamine Potassium Channel

- +/- - + ADHD + Pharmacology 9

α2 10 HCN (Funny) Norepinephrine Potassium Channel

 Antagonism of the alpha 2 receptor  We overwhelmed the alpha 2 receptor  Lead to ADHD symptoms  Lead to ADHD symptoms α2 α2 FILTER AND GAIN – PROVEN 11 PHARMACOLOGICALLY

Concentration Distraction DA & NE Levels 12 DA & NE Levels DA & NE Levels DA & NE Levels Low Normal High

Concentration ADHD Distraction DA & NE Levels 13 DA & NE Levels DA & NE Levels DA & NE Levels Low Normal High

 Family history (inheritable) & psychosocial  Temperamental  Environmental  Course modifiers ADHD – RISK FACTORS 14

 Inattention  Hyperactivity-Impulsivity  HYPERACTIVITY:  Fails to give close attention to details, makes careless mistakes  Fidgets with hands or feet or squirms in seat  Difficulty sustaining attention in tasks  Leaves seat in classroom or in other or play situations in which remaining seated is  Does not seem to listen when spoken expected to directly  Runs about or climbs excessively in situations in which it is inappropriate  Does not follow through on  Has difficulty playing or engaging in instructions, fails to finish schoolwork, leisure activities quietly chores, or duties  Is "on the go" or acts as if "driven by a  Difficulty organizing tasks and motor" activities  Talks excessively  Avoids, dislikes, or is reluctant to  IMPULSIVITY: engage in tasks that require sustained  Blurts out answers before questions mental effort have been completed  Loses things necessary for tasks or  Has difficulty awaiting turn activities  Interrupts or intrudes on others 15  Easily distracted by extraneous stimuli TYPES OF ADHD  Forgetful in daily activities

 Stimulants  Dextroamphetamine  Alpha agonists  Methamphetamine  Guanfacine (Intuniv)  Lisdexamfetamine (Vyvanse)  Norepinephrine re-uptake inhibitors  Dextroamphetamine +  Atomoxetine (Strattera) amphetamine (Adderall)  Methylphenidate (Ritalin)  Dexmethylphenidate (Focalin) MEDICATIONS USED TO TREAT 16

No outside stimulus is needed to initiate this process! HOW STIMULANTS WORK 17

 Dosage form  ADRs  Oral (XR or IR)  Hypertension, insomnia, headache, decreased appetite, dry mouth,  Kinetics abdominal pain, arrhythmia  Absorption – well absorbed, food  Interactions prolongs Tmax  CYP2D6 inhibitors, (bupropion &  Half life – 9-14 hours depending on fluoxetine), MAOI (CI), CNS age stimulants  Metabolism – Liver (CYP2D6) has  BBW – Cardiovascular disease & active metabolites abuse potential  Time to peak – IR (3 hours), XR (7  Pregnancy – C hours)  Excreted in breast milk  Excretion – urine (highly dependent on pH of urine, 30-75%) unchanged 18 drug, metabolites (50%) Dextroamphetamine + amphetamine - Adderall

 Dosage forms  Capsules  ADRs  Kinetics  Insomnia, decreased appetite, dry mouth, upper abdominal pain,  Absorption – rapid arrhythmia  Distribution – CNS penetration, CSF  Interactions concentrations 80% of plasma  MAOI (CI), CNS stimulants  Metabolism – In the blood, intestines, and liver (no CYP) -  Pregnancy – C Prodrug  Excreted in breast milk  Time to peak – about 1 hour  Excretion – 96% in the urine mostly as metabolites 19 LISDEXAMFETAMINE - VYVANSE

 Dosage forms  Capsules & tablets (XR, chewable, IR), solution & suspension, transdermal patch  Kinetics  ADRs  Absorption – readily absorbed  Insomnia, headache, decreased appetite, dry mouth, CV events (different dosage forms vary slightly)  Protein binding – low (10-33%)  Interactions  Metabolism – extensive, into inactive  MAOI (CI), Alcohol , CNS stimulants, compounds  Pregnancy – C  Half life – 2-7 hours, depending on  Excreted in breast milk dosage form and age  Time to peak – 1-11 hours, depending on dosage form and age  Excretion – 90% in urine as metabolites and unchanged drug METHYLPHENIDATE & DEXMETHYLPHENIDATE – RITALIN & 20 FOCALIN – RE-UPTAKE INHIBITOR

 Alpha agonists - guanfacine  Re-uptake inhibitors - Strattera α2 HOW THE OTHERS WORK - REVIEW 21

 Dosage forms  Tablet (XR, IR)  ADRs  Kinetics  Somnolence, dizziness, headache,  Absorption – Good fatigue, dry mouth, rebound hypertension (d/c)  Protein bound – 70%  Interactions  Metabolism – CYP3A4  CYP3A4 inhibitors, alcohol, other  Half life – 10-30 hours hypertensive medications,  Time to peak – 2.6-5 hours  Pregnancy – B  Excretion - 50% in urine as  Not known if excreted in breast milk unchanged drug 22 GUANFACINE – INTUNIV & TENEX

 Dosage forms  Capsule  ADRs  Kinetics  Somnolence/insomnia , headache, dry mouth, decreased appetite  Absorption – rapid  Interactions  Protein bound – 98%  CYP2D6 inhibitors, MAOIs (CI),  Metabolism – CYP2D6 (poor mifepristone, (QTc prolongation) metabolizers) & 2C19  Pregnancy – C  Half life – 5 hours (parent), 6-8 (metabolite)  Not known if excreted in breast milk  Time to peak – 1-2 hours (delayed by fatty meal)  Excretion – Urine, mostly as metabolites, 17 % in feces 23 ATOMOXETINE - STRATTERA

QUESTIONS 24