CNS stimulants- Joshi

What are the characteristic features of ADHD?

1. impulsiveness (acts quickly w/ minimal consideration of consequences)

2. hyperactivity (constant “verb” activities)

3. inattention (unable to focus)

Pts. with ADHD have an increased risk of what?

• developing other psych disorders

• maintaining relationships

• STDs/teen pregnancy

• major injuries

• drug abuse and addiction

What are the characteristic features of ADHD?

1. impulsiveness (acts quickly w/ minimal consideration of consequences)

2. hyperactivity (constant “verb” activities)

3. inattention (unable to focus)

Pts. with ADHD have an increased risk of what?

• developing other psych disorders

• maintaining relationships

• STDs/teen pregnancy

• major injuries

• drug abuse and addiction

A 10-year-old boy is diagnosed with attention-deficit hyperactivity disorder (ADHD). His doctor prescribes methylphenidate to improve his focus in school.

Which of the following best describes the mechanism of action of methylphenidate?

a. Inhibition of norepinephrine and dopamine reuptake

b. Increased serotonin release from presynaptic neurons

c. Direct activation of dopamine D2 receptors

d. NMDA receptor antagonism

a.

A 9-year-old girl with ADHD is started on dextroamphetamine. She was recently diagnosed with depression and prescribed phenelzine, an MAOIn, by a different doctor.

What is the most serious potential consequence of combining amphetamine with phenelzine?

a. Severe sedation and respiratory depression

b. Hypertensive crisis due to excessive catecholamines

c. Decreased stimulant efficacy due to drug competition

d. Serotonin syndrome

b.

What drugs can be used for ADHD therapy?

• psychostimulants

  • amphetamine, dextroamphetamine, methamphetamine

  • methylphenidate

  • modafinil

  • armodafinil

• non-stimulants

  • atomoxetine

What is the MOA of amphetamine, dextroamphetamine, and methamphetamine?

indirect-acting sympathomimetic drugs

• MOA inside axon terminal

  • increases release of catecholamines (DA, NE, 5-HT)

  • agonist at TAAR1 to decrease reuptake

  • weakly inhibits MAO-A

• MOA in synapse

  • prevents reuptake of DA and NE

KNOW BOLDED

Amphetamines are metabolized where and with what CYP?

metabolized by the liver through CYP2D6

What are the therapeutic effects of amphetamines?

• increased alertness and concentration

• euphoria

• decrease fatigue and appetite

• insomnia, HA

• dependence/abuse

• psychosis

• aggression, irritability, nervousness, tics

Misuse/abuse/overdose of amphetamines may lead potentially to what?

fatal cardiac ADRs

ADRs of amphetamines:

• CV

  • increased HR

  • HTN

  • arrhythmias

• GI

  • dry mouth

  • n/v/d

  • abdominal pain

• other

  • growth suppression

  • libido

WHAT ARE THE D/I with amphetamines?

• AVOID in pts. taking MAOIs (and within 14 days)

• AVOID alcohol while taking amphetamines

• absorption/ clinical effects increased by antacids

• absorption/ clinical effects decreased by vitamin C and acidic foods

amphetamines are pregnancy category __.

C.

How does methylphenidate compare to amphetamine?

• chemically? pharmacologically?

• which is superior?

• ADRs?

• chemically and pharmacologically like amphetamine

• considered superior to amphetamine for ADHD

• causes less tachycardia and growth retardation

ADRs of Methylphenidate:

• anorexia

• insomnia

• growth retardation

• abdominal discomfort

• bowel upset

MOA of modafinil?

exact unknown—> shows inhibition of NA and DA uptake, alters junctional concentration of glutamate and GABA

ADRs and WARNINGS of Modafinil:

• ADR: insomnia, anxiety, HA, n, dyspepsia, dizzy, confusion, amnesia, personality disorder, tremors, and HTN

• Warning:

  • pre-existing cardiac condition

  • hepatic/renal dysfunction

  • psychiatric disorders

  • Tourette’s syndrome

MOA of Atomoxetine:

selective NE reuptake inhibitor—> DOES NOT EFFECT DOPAMINE

Atomoxetine is metabolized by CYP___

2D6 (inhibits like fluoxetine and quinidine increase conc)

Atomoxetine is contraindicated in ___________.

glaucoma

Atomoxetine should not be used with _______.

MAOIs