8. Stimulants Flashcards
What are the 7 stimulants discussed in this part?
Natural:
Caffeine (methylxanthines)
Ephedrine
Synthetic: Atomoxetine Amphetamine (cocaine feeds into same thing as this) Modafinil Methylphenidate Phentermine
What is caffeine?
Structure, metabolized by, 2 mechanisms
Xanthine core with 3 methyl groups (depending what methyl group you remove you can get theophylline)
Metabolized by liver (CYP450)
Half life of 6 hours
Increased cAMP leads to stim effect
Both water and lipid soluble so easily crosses BBB
Mechanisms:
Adenosine receptor antagonist (indirectly increases acetylcholine release)
Inhibits phosphodiesterase which leads to increase cAMP
Slides 5-6
What are amphetamines?
Half life, mechanisms
Structurally related to NE and dopamine
Half life of 20 hours
Mechanisms:
Increase neuromodulator levels (stimulates release and blocks reuptake of NE and DA with lesser effects on 5-HT
Inhibits MAO- inhibit degradation of the neuromodulators as well
Slide 7
What is methylphenidate?
Half life, mechanism
Half life of 2 hours (better to work with)
Ritalin is a methylphenidate
Mechanism:
Blocks reuptake of DA and NE
Slide 7
What is atomoxetine?
Half life, treats?, mechanisms
Approved treatment for ADHD
Half life 5-20 hours
Mechanisms:
Inhibits NET, SERT, DAT
NMDA receptor antagonist
Slide 8
What is modafinil?
Half life, treats?, mechanisms
Wakefulness-promoting agent
Approved for treatment of narcolepsy
Half life is about 10-12 hours
Mechanisms of action remain unclear
- elevates hypothalamic histamine levels (wakefulness promoting, antihistamines make you drowsy)
- inhibits DA reuptake
What is phentermine?
Half life, mechanisms
Excreted unchanged by kidneys
Well tolerated
Available in immediate and sustained release formations
Half life of 2 hours (10 for sustained release)
Mechanisms:
Promotes NE and DA release
Suppress appetite through satiety center hypothalamus (can be used as anti-obesity agent)
Slide 9
What is ephedrine?
Half life, mechanisms
Half life of 3-4 hours
CNS stimulant similar to amphetamines
Mechanisms:
Sympathomimetic acting on SNS
Indirectly increases activity of NE on adrenergic receptors
Slide 9
What are the adverse effects of amphetamines?
Insomnia Potential for addiction Vertigo Hypertension Confusion Nausea Diarrhea
Focus on top two
What is narcolepsy?
Neurological disorder that has sleep attacks (enter REM sleep instantly during day), excessive daytime sleepiness (EDS), hallucinations as falling asleep or waking up, loss of muscle tone occurs without loss of consciousness in response to strong emotions
Cause is unknown (some ppl have reduced amount of protein called hypocretin/orexin with narcolepsy
Slides 12-13
How do you treat narcolepsy?
The stim drug armodafinil (R enantiomer of racemic modafinil) tried first (much less likely to be abused than other stims)- best absorbed in empty stomach
Other stimulants include dextroamphetamine (Dexedrine) and methylphenidate
Slide 14-15
What is attention deficit hyperactivity disorder (ADHD)?
Most common diagnosed behavioural disorder of childhood
Girls have inattentive/distractable symptoms
Boys have impulsive/hyperactive symptoms
How do you treat ADHD?
Combination of medication and behavioural treatment works best
Psychostimulants/stimulants are the most commonly used ADHD drugs
Calming effect on people with ADHD
Drugs used: Amphetamine-dextroamphetamine (adderall) Dexmethylphenidate (focalin) Dextroamphetamine (Dexedrine) Lisdezamfetamine (vyvanse) Methylphenidate (Ritalin)
