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PHRM 845 > 4.7 Pathophysiology of ADHD, pharmacology of stimulants > Flashcards

4.7 Pathophysiology of ADHD, pharmacology of stimulants Flashcards

1
Q

What causes the majority of ADHD?

A

Heritable (genetics)

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2
Q

What are the implicated systems in ADHD?

A
  • DA transporter, COMT, cholinergic receptors
  • Cholesterol metabolism, CNS development, glutamate receptors
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3
Q

What are clinical presentations of ADHD?

A
  • Sxs at ages 5-9 yo (generally before 12 for diagnosis)
  • 6 or more sxs must be present
  • Significant impairment in 2 or more settings
  • Sxs documented by parent, teacher, and clinician
  • Interferes w functioning and development
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4
Q

What are the clinical sxs of ADHD?

A
  • Inattention: difficulty organizing tasks, easily distracted
  • Hyperactivity
  • Impulsivity
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5
Q

What is the possible circuity mechanism as to why the sxs of ADHD are what they are?

A

Medial prefrontal cortex (mPFC) control might not be fully functional

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6
Q

What type of stimulant is methylxanthines?

A

Indirect acting sympathomimetics

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7
Q

What are indirect acting sympathomimetics?

A

Stimulant compounds that mimic the effect of endogenous agonists of sympathetic nervous system

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8
Q

What do methylxanthines do?

A
  • Antagonize adenosine receptors
  • Inhibit phosphodiesterases: increase cAMP (potentiate Gs linked receptors)
  • Increase activity of ryanodine receptors, increasing intracellular Ca2+
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9
Q

What is the A1 (adenosine) receptor linked to?

A

Gi/o linked

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10
Q

What does the A1 receptor do?

A

Inhibitory modulation of many neurotransmitters

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11
Q

Where are A1 receptors located?

A

Cerebral cortex, hippocampus, cerebellum, thalamus, brain stem, spinal cord

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12
Q

Activation of A1 receptors in the CNS can cause:

A

Sedation, anxiolysis, anticonvulsant activity

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13
Q

Activation of A1 receptors in the periphery can cause:

A

Decreased HR

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14
Q

What is A2a receptor linked to?

A

Gs linked

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15
Q

Where are A2a receptors located?

A

Cerebral vasculature, striatum

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16
Q

What are A2a receptors responsible for?

A

Vasodilation

17
Q

Which adenosine receptors are heterodimers of A1 and D2 receptors?

A
  • A2b
  • A3
18
Q

What is the A2b receptor linked to (hint: same as A2a)?

A

Gs linked

19
Q

Where are A2b receptors located and what is its function?

A
  • Glial cells
  • Function unknown
20
Q

What is the A3 receptor linked to?

A

Gq linked

21
Q

Where are A3 receptors located?

A

Hippocampus and thalamus

22
Q

When are A3 receptors activated?

A

Only activated in states of excessive catabolism (e.g. seizures, hypoglycemia, stroke)

23
Q

Are A3 receptors antagonized by methylxanthines?

A

No

24
Q

What is the effect of methylxanthines?

A
  • Increased alertness
  • Decreased fatigue
25
Q

What are monoamines?

A

DA, NE, 5HT

26
Q

What type of stimulant is cocaine?

A

Indirect acting sympathomimetics

27
Q

What is the MOA of cocaine?

A

Inhibit (blockade only) monoamine transporters (NE, 5HT, DA)

28
Q

What is cocaine used clinically?

A

Local anesthetic

29
Q

What type of stimulant are amphetamines?

A

Indirect acting sympathomimetics

30
Q

What is the MOA of amphetamines?

A

Non-selective activation of monoamines

31
Q

What is the one exception to amphetamines MOA?

A

Ecstasy, which is more selective for 5HT

32
Q

What are effects of amphetamines?

A

Wakefulness, alertness, increased ability to concentrate

33
Q

High doses of amphetamines can cause what?

A

High doses can elicit psychotic behaviors

34
Q

What drugs are amphetamines?

A
  • Dextroamphetamine (dexedrine), lisdexamfetamine (vyvanse)
  • Methylphenidate
  • Adderall
  • Mydayis
35
Q

What are amphetamines used for?

A

Narcolepsy, anorexiant/weight loss, ADHD

36
Q

What are the non-stimulants for ADHD?

A
  • Atomoxetine (stratterera): a NET inhibitor for adult
  • TCAs (tricyclic antidepressants)
  • Bupropion (wellbutrin)
  • Clonidine (catapres)/guanfacine (tenex)
37
Q

What are alternative therapies for ADHD?

A
  • Elim artificial food additives, colors, preservatives
  • EEG biofeedback
  • Essential FA supp
  • Yoga/massage
  • Green outdoor spaces
38
Q

What is narcolepsy?

A
  • Excessive daytime sleepiness
  • Cataplexy/weakening of muscles
  • Poor quality of sleep
  • Sleep paralysis
  • Hypnogogic hallucinations
39
Q

What are txs for narcolepsy?

A

Stimulants for sleepiness:
- Solriamfetol (sunosi): MOA on NET and DAT
- Modafinil (provigil)
- Antidepressants
- Xyrem (GHB)
- Pitolisant: histamine3 receptor antagonist

PHRM 845 (48 decks)

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