10/17 CNS Stimulants - Welsh

Question 1

ADHD keys

Answer 1

attention deficit and hyperactivity disorder: characterized by developmentally inapprop levels of…

1. inattention
2. hyperactivity
3. impulsivity

• M:F = 2:1
• familiar → higher risk if family member affected
• assoc with reduced frontal lobe volume/metabolism
• can persister into adulthood

Question 2

treatment of ADHD

Answer 2

• behavioral tx/modification
• stimulants (methylphenidate, mixed amphetamines): improve behavior and learning in 60-80% of correctly diagnosed children
  
  • 10-30% of ADHD pts are stimulant-resistant
• alternatives
  
  • ​non-stimulants: atomoxetine, guanfacine, clonidine
  • antideps: fluoxetine (Prozac), bupropion (Welbutrin)

Question 3

pharmacologic tx for ADHD

Answer 3

**tx of children and YAs requires v diff approach from adults

1. stimulants (first line therapy)

• methylphenidate (Ritalin), dexmethylphenidate
• mixed amphetamine salts, dextroamphetamine (Adderall)

2. non-stimulants (generally inferior to stimulants)

• atomoxetine (NE reuptake inhibitor)
  
  • better suited to adolescent and adults (2+wk time lag before effects)
• guanfacine, glonidine (alpha2 adrenergic agonists) → stimulate alpha2 adrenergic receptors in prefrontal cortex (enhance executive fx, attentiveness, working memory)
• bupropion and TCAs (DA and NE reuptake inhibitors)

these drugs used as adjuncts to stimulants or when stimulant side effects are intolerable

have little/no abuse potential

Question 4

stimulants: mechanism of action

Answer 4

overall: enhance monoamine activity

• methylphenidate
  
  • inhibits reuptake of NE and DA
  • mild inhibitor of MAO
• amphetamine
  
  • blocks reuptake of DA
  • block storage vesicles → increased releaseof presyn NE and DA
  • mild inhibitor of MAO

Question 5

common adverse effects of stimulands & management

Answer 5

Question 6

4 major clinically used stimulants

Answer 6

methylphenidate

amphetamine

methamphetamine

cocaine

Question 7

substance use/abuse disorders

Answer 7

self administration of a drug for prolonged periods or in excessive amounts → physical and/or psychological dependence

most drugs of abuse affect the CNS

ex.

• alcohol
• CNS depressants (narcotic analgesics, arijuana)
• CNS stimulants (cocaine, ecstasy, methamphetamine, nicotine)
• hallucinogens (LSD)

Question 8

cocaine

mechanism

effects

side effects

what happens with high dose, chronic use?

addictiveness

Answer 8

powerful CNS stimulant

• mechanism: inhibits reuptake of DA, NE, 5HT
• euphoria, incr sympathetic drive
  
  • incr energy/alertness
  • tachycardia
  • vasoconstriction
  • incr bp
  • restlessness
  • mydriasis
  • hyperthermia
• wearing off → depression, fatigue, drowsiness

side effects: cardiac dysrhythmias, MI, seizures, stroke, death

high-dose, chronic use: toxic paranoid psychosis, aggressive homicidal behavior

addictiveness: not physically addictive, BUT causes psych dependence

Question 9

mechanism of action: cocaine, amphetamines

Answer 9

both act as sympathomimetics → stimulate SNS

• cocaine
  
  1. blocks DA, NE, 5HT reuptake transporters (DAT, NET, SERT) → incr nt levels and activity in synapse
• amphetamine
  
  1. substrate for DAT → inhibits DA reuptake
  2. blocks vesicular monoamine transporter (VMAT) → incr release of DA into synapse

peripherally, adrenergic effects activate SNS “fight or flight” syndrome

Question 10

PK: cocaine

absorption

distribution/metabolism

Answer 10

absorption (fast → slow)

• IV
• intranasal
• oral
• smoked

distribution/metabolism

• rapidly crosses BBB
• rapid enzymatic breakdown (pl halflife 60min)
• crosses placenta
• can mix with uppers and downers
  
  • cocaine + alcohol = cocaethylene (v psychoactive)
  • cocaine + heroin = speedballing (intense euphoria)

Question 11

treatment of cocaine addiction and OD

OD/addiction tx

symptoms → how to manage

effects of withdrawal

Answer 11

no antidote for OD, no approved safe/effective tx for addition

sx: agitation, HTN, tachycardia, psychosis/hallucinations, hyperthermia, MI, seizures, coma, death

• psychosis → antipsychotics (haloperidol, chlopromazine)
• cardiac dysrhythmias → antidysrhythmics
• anx/dep: anxiolytics, antidepressants
• seizures, nausea, irritability → benzodiazepines (diazepam, lorazepam)

effects of withdrawal: apathy, anx/irritability, disorientation, depression

• need detox and psych counseling

Question 12

methamphetamines and related amphetamines

approved uses

mech of action

effects/addictiveness

Answer 12

aka “poor man’s cocaine”

approved uses: ADHD, narcolepsy, weight reduction

mechanism of action: incr DA, NE, 5HT neurotransmitters

• fast CNS penetration

effects

• immediate stimulation, euphoria → higher potential for addiction/abuse
• dose-related effects with development of tolerance
  
  • low doses: mental alertness, wakefulness, incr energy
  • high doses: psychoses, oral damage (“meth mouth”)
• crosses placenta

Question 13

meth vs cocaine

Answer 13

produce similar acute and chronic effects

• mydriasis, euphoria, grandiosity, paranoia, psychosis, tachycardia, hyperthermia, hypertension, loss of appetite, insomnia
• severe hyperthermia? cocaine more common

half-life

• cocaine: 1-2hr
• meth: 8-12hr

paranoia

• cocaine: 4-8hr following cessation
• meth: 7-14days
  
  • ​meth psychosis may req medication/hospitalization, may be irrev

OD: severe convulsions → cardiovascular/resp collapse, coma, death

Question 14

pharmacotherapies: meth/cocaine

tx of addiction vs withdrawal

Answer 14

treatment of addiction

• no approved safe/effective tx for meth addiction
• best tx: prevention
• next best: CBT
• vaccines and abs for cocaine and meth are under devpt

treatment of withdrawal

• meth withdrawal similar to cocaine, but longer duration
• alpha1 adrenergic antagonists (prazosin) can relieve withdrawal sx
• antipsychotics (chlorpromazine, lahoperidol)
• anxiolytics (lorazepam, diazepam) for anxiety, seizures
• antideps (fluoxetine, desipramine) for depression