L15- CNS Stimulants

What are psychomotor stimulants used to treat?

• attention deficit disorder (ADD) / attention deficit hyperactivity disorder (ADHD)

• narcolepsy

What is the goal of using psychomotor stimulants for ADD/ADHD?

increase dopamine and norepinephrine levels → get PTs to a level that is neurotypical → improve focus

What are the medications used to treat ADD/ADHD?

• stimulants

  • amphetamine

  • lisdexamfetamine

  • methylphenidate

• selective norepinephrine reuptake inhibitor

  • atomoxetine

What medication is a non-stimulant treatment for ADD/ADHD?

atomoxetine

The following symptoms are all indications of ____________________:

• difficulty sustaining wakefulness

• poor regulation of REM sleep

• disturbed nocturnal sleep

• excessive daytime sleepiness

Narcolepsy

What is nacrolepsy caused by and is there a drug to correct this?

• loss of orexin-producing hypothalmic neurons (wake-promoting neurons)

• no; there is currently no therapeutic to directly address this causation

What medications are used to treat narcolepsy?

• modafinil

• armodafinil

List the catecholamines

• dopamine

• norepinephrine (derived from dopamine)

• epinephrine

Dopamine and norepinephrine are eliminated from the synapse primarily by ____________

reuptake

• recycled into synaptic vesicles OR

• metabolized into inactive metabolites

In general, how do catecholamine releasers work?

disrupt catecholamine release or reuptake

List catecholamine releasers

• amphetamine

• lisdexamfetamin

What is the MOA for amphetamine?

stimulates presynaptic release of dopamine and norepinephrine (catecholamines)

In general, how do reuptake inhibitors work?

methylphenidate-like sympathomimetics block reuptake transporters and inhibit dopamine/norepinephrine reuptake from synapse

List reuptake inhibitors

• methylphenidate

• atomoxetine

• bupropion

• cocaine

Which reuptake inhibitor has a local anesthetic action?

cocaine

• voltage-gated Na+ channel inhibitor

Which “atypical” reuptake inhibitor is used to treat narcolepsy?

modafinil

What are the adverse central nervous system effects for psychomotor stimulants?

acute toxicity: psychotic symptoms (paranoia, hallucinations)

• headaches, dizziness, tremor, increased irritability, insomnia

• panic states, anxiety, confusion, aggressiveness, delirium

What are the adverse cardiovascular effects for psychomotor stimulants?

acute toxicity: increase in blood pressure and heart rate

• direct activation of beta-1 adrenergic receptors on the heart

• can cause palpitations, chills, cardiac arrhythmia, chest pain/agina

• xerostomia (dry mouth) caused by vasoconstriction and lack of salivation → risk of tooth decay

______________ are an absolute contraindication for psychomotor stimulants

Monoamine oxidase inhibitors (MAOIs)

Psychomotor stimulants have been shown to cause extensive psychological dependence, meaning they are _______________

highly addictive

T/F: the major problem with psychomotor stimulants is getting PTs to withdraw/detox

False; major problem is to help PTs resist the urge to retart compulsive use (cravings)

_____________ are non-psychomotor stimulants (drugs that produce a stimulant through a non-psychomotor mechanism)

Methylxanthenes

What is the MOA for methylxanthenes?

inhibits enzyme phospdiesterase

• increases intracellular cAMP → increases HR & BP

List the methylxanghenes

• Theophylline — long acting

• caffeine — intermediate-acting

What are the adverse efefcts for methylxanthenes?

• moderate dose — headache, nausea/vomiting, insomnia, anxiety, agitation, diuresis

• high dose — cardiac arrhythmia, seizures

______________ is a CNS stimulant that is a nicotinic acetylcholine receptor agonist with a short duration of action

Nicotine

Is withdrawal or relapse the primary problem with nicotine?

withdrawal

________ is a nicotine abstincence therapy drug indicted for cravings associated with cessation

buproprion

___________ is the most effective nicotine abstinence therapy drugs

Varenicline

What is the MOA for varenicline?

partial agonist of nicotinic acetylcholine receptors

• helps replace cravings while blocking nicotine effects by competing for receptors → reduces withdrawal effects

• Review: a partial agonist acts as an antagonist in the presence of a full agonist