Stimulants

Question 1

What are the ‘desired’ effects of sympathomimetics?

Answer 1

• Decreased fatigue
• Increased wakefulness, alertness, initiative, confidence, ability to concentrate, motor & speech activity
• Improved simple activity and athletic performance

Organ effects:

• Increased systolic and diastolic BP
• High doses cause arrhythmias
• Palpitations, anginal pain, circulatory collapse, & hyperthermia

Question 2

What are the CNS effects of sympathomimetics?

Answer 2

Acute: dizziness, agitation, confusion, insomnia, seizures

Chronic: amphetamine psychosis: vivid hallucinations, paranoid delusions and compulsions, marked weight loss, resolve in 7-10 days

Question 3

What is the mechanism of action of sympathomimetics (all the same except MDMA aka ecstasy)?

Answer 3

Low dose: Increased release of NE and DA
Medium dose: Blocks NE & DA reuptake
High dose: inhibits monoamine oxidase

Ecstasy: directly stimulates 5HT 21A receptors - binds to norepinephrine transporter protein. Added methyl group to increase lipophilicity and thus easier access to brain

Question 4

What are the pharmocokinetics of sympathomimetics?

Answer 4

• Amphetamine and Methylphenidate: tolerance develops to effects on appetite and mood; abrupt withdrawal results in craving, prolonged sleep, fatigue, eating
• Cocaine: withdrawal effects consistently occurs with cocaine little tolerance
• MDMA (ecstasy): Stimulates release & inhibits reuptake of serotonin, epi, NE, and DA

Question 5

What are the sympathomimetics?

Answer 5

• Amphetamine (Benzedrine)
• Methylphenidate (Ritalin)
• Cocaine
• MDMA (ecstasy)

Question 6

Bath salts (mephedrone)

Answer 6

• Act in brain as “cocaine substitutes”
• Often contain various amphetamine like substances
• High abuse and addiction liability

Question 7

What are the effects and mechanisms of Xanthines (caffeine and theophylline)?

Answer 7

• Stimulate cortex: clearer though, less fatigue, increased dexterity
• Medullary centers: stimulate respiratory & vasomotor center
• Smooth muscle relaxant (decreased peripheral vascular resistance, increase cerebral vascular resistance)
• Withdrawal: headache, irritibility, inability to concentrate, insomnia
• theophylline higher potency than caffeine
• LD50 of caffeine is 150-200 mg/kg ~80-100 cups of coffee

Question 8

What are the effects and mechanisms of eugeroics (Modafinil & armodafinl)?

Answer 8

• Treats narcolepsy and shift work sleep disorder (promoted as wakefulness agent); effective for ADHD
• CNS effects: headache, insomnia, dizziness, agitation, anxiety
• Can cause nausea, lack of appetite, high BP, severe derm reactions
• Elevates hypothalamic histamine levels, activates glut circuits, inhibits GABA transmission. Increases DA & NE