Psychostimulants Flashcards
Amphetamine MOA
Agonists of monoamine neurotransmitters
Mainly promote RELEASE of biogenic amines from storage sites by INHIBITING VMAT
Normally VMAT functions to store DOPAMINE in intracellular vesicles
-> By inhibiting VMAT you force Dopamine and Norepinephrine to be more freely available in the cytosol for release from presynaptic neurons
Main Concerns when prescribing Amphetamines and Amphetamine-like agents
1) Stimulant effects on
CNS, GI, Cardiovascular
2) Psychosis With high doses
3) Psychological dependence
4) Withdrawal reactions
- > Depressed mood, fatigue
Main effect of Norepinephrine release triggered by ADHD drugs
Stimulation of Alpha 1 Receptors
- > Alpha 1 Adrenergic Receptor activation leads to Vasoconstriction
- > Increases systemic vascular resistance -> blood pressure goes up as a result
Management of Overdose with ADHD medications
1) Control cardiovascular hemodynamics
- > Eg, Alpha blockers (Cause VASODILATION), Nitrates
2) Sedatives
- > Eg, benzodiazepines
3) Activated charcoal
Methylphenidate
= Ritalin
- > Most commonly used Amphetamine
- > you are less concerned about cardiovascular effects vs. other amphetamines because Ritalin causes less release of Norepinephrine into the periphery (thus lower risk of Cardiovascular effects like high BP and potential infarction)
Schedule II drugs (like Vyvanse, ADHD drugs)
1) Prescribed in restricted quantities
2) Must be filled within specific number of days
3) Have Signature & DEA number
4) Telephone for emergencies only
Atomoxetine (Strattera)
Mechanism:
Selective INHIBITOR of norepinephrine transport (Inhibitor of NE reuptake -> NE stays in the Synaptic cleft for longer)
Extensive HEPATIC metabolism (CYP 2D6)
Schedule IV drug
Concerns: SUICIDE in a smaller number of patients
1) CNS
2) GI
3) Cardiovascular
Others:
- Dry mouth, urinary retention
- Priapism (painful, prolonged ERECTIONS)
- Drug interactions
Guanfacine (Intuniv -> DRUG DAT DONT MAKE NO SENSE)
MOA: Centrally acting Alpha-2 receptor AGONIST
-> (MOA for ADHD UNCLEAR)
Main side effects:
1) Sedation
2) Hypotension
Schedule IV drug
COUNTERINTUITIVE MOA: Other ADHD drugs cause more release of Norepinephrine, but this drug activates the auto-inhibitory Alpha-2 receptor pathway, which leads to lowered production of Catecholamines ‘ (like NE and Epinephrine)
Similar MOA to Clonidine (used to lower BP)
Caffeine and Adenosine
Caffeine is an Adenosine Receptor ANTAGONIST
-> (opposite effect as Adenosine)
Adenosine suppresses CNS activity
Pharmalogical Effects of Caffeine
1) Increased arousal & alertness
2) Cardiac & smooth muscle effects
3) Anorexia
4) Diuresis
Mechanism:
Adenosine receptor antagonist
Effects of Adenosine on Presynaptic and Postsynaptic Neurotransmission
Adenosine has both presynaptic and postsynaptic effects on neurotransmission
Presynaptic:
- Closes Ca++ channels
- Lowers NT release
Postsynaptic:
- Opens K+ channels
- Hyperpolarizes postsynaptic neuron
Theophylline
A metabolite of Caffeine that is like a SUPER-caffeine
-> (you need to MONITOR blood levels of Theophylline because at high levels this can be dangerous)
Like Caffeine, Theophylline causes Vasoconstriction
Form of Caffeine that is used in Excedrin
Concerns about Excessive Caffeine Production
1) CNS
2) GI
3) Cardiovascular
4) Tolerance & withdrawal
5) Guarana & presence in supplements
- > Plant that has a lot of caffeine
Modafinil (Provigil) AND armodafinil (Nuvigil) MOA:
- Blocks dopamine transporter (Inhibits Dopamine Reuptake)
- > Increases synaptic dopamine
Used for excessive sleepiness:
- Narcolepsy
- Shift work
- Obstructive sleep apnea
Schedule IV drug
Gamma-Hydroxybutyrate (GHB)
DATE RAPE DRUG
MOA:
Exhibits Dopamine-like effects and GABA-like effects
AKA: Sodium oxybate (Xyrem)
Used for:
1) Cataplexy (strong emotion or laughter causes a person to suffer sudden physical collapse though remaining conscious)
2) Refractory NARCOLEPSY
Schedule III drug
-> If a child takes even a little bit of this medicine, it could cause DEATH
