PHARM - CNS Stimulants

Question 1

list the indications of CNS stimulants

Answer 1

1. ADHD
2. narcolepsy
3. obesity

Question 2

list the primary effects of CNS stimulants

Answer 2

• elevation of
  
  • mood (aka euphoria)
  • wakefulness / alertness
  • self confidence / initiative
  • talkativeness
  • respiration
• reduction of
  
  • fatigue
  • appetite

Question 3

list the CV effects of CNS stimulants

Answer 3

• increase in - BP & respiratory rate
• possible decrease in - HR
• arrythmias

Question 4

what behaviors characterize ADHD?

Answer 4

three behavioral presentations:

• inattention
• hyperactive-impulsive
• combinated inattention + hyperactive impulsive

Question 5

describe the mechanism behind ADHD

Answer 5

• ADHD is due to impaired pre-frontal cortex function, which requires
  
  1. optimal levels of NE to act at post-synaptic a2 adrenegic receptors
  2. optimal levels of DA to act at D1 receptors
• imbalance / insufficiency of these NT-receptor interactions = ADHD

Question 6

what is the primary mechanism by which ADHD is treated pharmaceutically?

what effects does this treatment have?

Answer 6

via stimulation of pre-frontal a2 adrenergic receptors, which:

• strengthens pre-frontal cortex behavior regulation
• reduces distractability
• increases locomotion (at high doses)

Question 7

methylphenidate

• what kind of drug?
• includes what drugs?
• indication
• MOA
• key AEs

Answer 7

• drug type: CNS stimulant
• includes:
  
  • ritalin
  • concerta
  • focalin (dexmethylphenidate)
• indication: ADHD
• MOA: block DA > NE reuptake by blocking their transports (DAT, NET)
• adverse effects:
  
  • insomnia
  • growth suppression

Question 8

amphetamines

• are what kind of drug?
• includes what drugs?
• indication
• MOA
• key AEs

Answer 8

• drug type: CNS stimuilant
• include:
  
  • adderal (amphetamine mixture)
  • vyvanse (L-lysine-D amphetamine)
• indication: ADHD
• MOA: block NE & DA reuptake by blocking their transports (NET, DAT)
• adverse effects:
  
  • insomnia
  • growth suppression

Question 9

are metnhylphenidates or amphetamines used more for ADHD?

why?

Answer 9

methylphenidates (ritalin, concerta, focalin)

lower doses are required for efficacy, and they are less frequency abused

Question 10

why can ADHD CNS stimulants cause growth suppression?

what are means to counter this AE?

Answer 10

• because they stimulate the lateral hypothalmic feeding area which suppresses appetite → producing anorexia → limiting growth
• this can be somehwat countered if pt
  
  • takes the drug during / after meals
  • takes drug holidays (controversial)

Question 11

CNS stimulants are what schedule drug?

Answer 11

schedule II

Question 12

at higher than prescribed doses, CNS stimulants can cause what AEs?

Answer 12

• meth mouth
• physical dependency
• psychosis

Question 13

review the mechanism by which ADHD CNS stimulants would lead to addiction

Answer 13

by activating the brain’s reward circuitry system

• amphetamines / methylphenidates → increase DA levels
• DA → stimulates VTA
• VTA → releases DA onto nucleus accumbens
• nucleus accumbens → induces feelings of pleasure

Question 14

which non-stimulant drugs can be used to treat ADHD?

Answer 14

• atomoxetine (NE reuptake inhibitor)
• clonidine (a2 adrenergic agonist)
• guanfacine (a2 adrenergic agonist)

Question 15

atomoxitine

• what kind of drug
• MOA
• PK
• AEs

Answer 15

• drug type: non-stimulant ADHD drug
• MOA: selective NE reuptake inhibitor
• PK:
  
  • metabolized by CYP-2D6
  • both acute / delayed onset
• AE: suicidal ideations ​

Question 16

gaunfacine

• what kind of drug
• MOA
• AEs

Answer 16

• drug type: non-stimulant ADHD drug
• MOA: selective a2 adrenergic receptor agonist
• AEs: (d/t inhibited vasoconstriction)
  
  • bradycardia
  • hypotension
  • syncope
  • heart block

Question 17

clonidine

• what kind of drug
• MOA
• AEs

Answer 17

• drug type: non-stimulant ADHD drug
• MOA: selective a2 adrenergic receptor agonist
• AEs: (d/t inhibited vasoconstriction)
  
  • bradycardia
  • hypotension
  • syncope
  • heart block

Question 18

guanaficine & clonidine are are cautioned in patients who__?

Answer 18

have experienced bradycardia, hypotension, syncope, or heart block

Question 19

which ADHD drug is heavily metabolized by CYP-2D6?

what is this important?

Answer 19

atomoxetine (non-stimulant ADHD drug)

atomoxetine typically has a 5 hr half life, but in CYP-2D6 PMs (poor metabolizers) can last > 24 hrs.

thus, CYP-D26 PMs should receive l_ower atomoxetine doses_

Question 20

which CNS stimulants can be used for weight loss?

Answer 20

• phentermine
• phentermine / topiramate

(amphetamines are NOT recommended for weight loss)

Question 21

phentermine

• what kind of drug
• indication
• MOA
• AEs

Answer 21

• drug type: stimulant
• indication: weight management
• MOA: induces catecholamine release at hypothalamus → reduced appetite
• AE: potential abuse

Question 22

phentermine/topiramate

• what kind of drug
• indication
• MOA
• AE/CI

Answer 22

• drug type: combination stimulant
• indication: weight management
• MOA: phentermine i_ncreases catecholamines_ at hypothalamus
  
  • (MOA of topiramate unknown)
• AE/CI: teratogenic / CI in pregnancy

Question 23

what steps must be taken before placing patient on phentermine / topiramate?

why?

Answer 23

female patients must be

• pregancy tested
• on contraception

topiramate component is teratogenic

Question 24

what is narcolepsy?

review the basic mechanism behind narcolepsy.

Answer 24

narcolepsy = the loss of sharp transitions between wake and sleep

d/t a loss of orexin producing neurons; orexin stimulates wakefulness promoting neurons in the cortex, brainstem, and basal forebrain

Question 25

modafinil

• indication
• MOA
• PK
• schedule
• AEs

Answer 25

• indication: first line for narcolepsy
• MOA: unknown
• PK: metabolized by CYP-3A4
• schedule: IV
• AEs:
  
  • heachaches*
  • chills, back pain, nausea (less frequent)