CNS Stimulants (Welsh) - 10/17/16 Flashcards
Treatment of ADHD
- Behavioral therapy/modification
-
Stimulants (first line therapy):
- Methylphenidate (Ritalin)
- Mixed amphetamines salts, Dextroamphetamine (Adderall)
-
Non-stimulants:
- Atomoxetine
- NE reuptake inhibitor
- Better suited to adolescents and adults since 2+ week lag time before effects appear
- Guanfacine
- alpha 2 adrenergic agonist: stimulation of alpha 2 adrenergic receptors in prefrontal cortex enhances executive functioning, attentiveness, working memory
- Clonidine
- ” “
- Atomoxetine
-
Anti-depressants:
- Fluoxetine (Prozac)
- Buproprion (Welbutrin)
- DA and NE reuptake inhibitors
Stimulants: Mechanism of Action
Amphetamines can gain entry into neuron. By gaining entry, will travel up and block storage vesicles → leading to depletion of NE and DA → increased release of presynaptic NE and DA
- Inhibit reuptake of NE & DA → enhance monoamine activity
- Block storage vesicles → cause increased release of presynaptic NE and DA
RESULT: enhance monoamine activity (increased DA activity in synapse)
Stimulant Adverse Effects and Their Management
Common Adverse Effects
- Reduced appetite, weight loss
- Stomach Ache
- Insomnia
- Headache
- Rebond symptoms
- Irritability/jitterness
Management Strategy
- Reduced appetite, weight loss
- Give high-calorie meal when stimulant effects are low
- Stomach Ache
- Administer stimulant on full stomach; lower dose if possible
- Insomnia
- Give dose earlier in the day; lower the last dose
- Prescribe a sedative at bedtime
- Guanfacine
- Clonidine
- Melatonin
- Headache
- Divide dose, give with food, or give an analgesic
- Rebound symptoms
- Consider longer-acting stimulant
- Irritability/jitterness
- Assess for comorbid condition (e..g., bipolar disorder); reduce dosage; consider mood stabilizer or atypical antipsychotic
Clinical Uses of Stimulants
- Drug name
- Trade name
- Street name
- CSA
- Indications
CNS depressants vs CNS stimulants
Depressants:
narcotic analgesics, marijuana
Stimulants:
cocaine, ecstasy, methamphetamine, nicotine
Cocaine
- Powerful CNS stimulant
- Topical anesthetic (like lidocaine, novocaine, etc…)
- Inhibits reuptake of DA, NE, and serotonin (5-HT)
Effects:
- Produces euphoria
- Increases sympathetic drive: inc. E and alertness, tachycardia, vasoconstriction, inc. BP, restlessness, mydriasis, hyperthermia
What happens as cocaine wears off?
As drug wears off, patient feels depressed, fatigued, drowsy.
High-dose: chronic use → toxic paranoid psychosis, aggressive homicidal behavior
Not physically addictive but causes psychological dependence
“Crack” cocaine (free base) highly addictive after first dose
Compare & Contrast the mechanisms of actions:
COCAINE and AMPHETAMINE
Both act as sympathomimetics (stimulate the sympathetic nervous system).
Cocaine blocks DA, NE, and 5‐HT reuptake transporters (DAT, NET, SERT) ⇒ thereby ↑ neurotransmitter levels and activity in synapse.
Amphetamine = substrate for DAT (gains entry into presynaptic neuron, blocks specific monoamine transporter) ⇒ inhibits DA reuptake
- Also blocks vesicular monoamine transporter (VMAT), thereby increasing release of DA into synapse.
- Peripherally, their adrenergic (NE) effects activate the sympathetic “fight or flight” syndrome.
- May be more dangerous than cocaine in terms of surge of euphoria (1/2 life is longer too)
Pharmacokinetics of Cocaine
Distribution and Metabolism
- Rapidly crosses BBB
- Rapid enzymatic breakdown; plasma 1/2 life ~60 min
- Freely crosses placenta (“crack babies”)
- Mixing uppers + downers:
- cocaine + alcohol = cocaethylene (psychoactive);
- cocaine + heroin = speedballing (intense euphoria)
- misguided attempt to reduce respiratory depression risk associated w/ opioid intake
Treatment of Cocaine Addiction and Overdose
No antidote for OD
No approved, safe and effective, treatment of addiction.
Treat symptoms
- Psychosis:
- antipsychotics (haloperidol, chlopromazine)
- Cardiac dysrhythmias:
- antidysrhythmics
- Anxiety/depression:
- anxiolytics/antidepressants
- Seizures, nausea, irritability:
- benzodiazepines (diazepam, lorazepam)
Need detox and psychiatric counseling
Methamphetamine and related amphetamines
- Approved uses
- Neurotransmitter action
- CNS crossing capability
- Low dose effects vs high dose effects
- Placenta crossing capability
aka poor man’s cocaine (cheaper, much easier to get on the street)
- Approved uses:
- ADHD, narcolepsy, weight reduction
- Neurotransmitter action:
- Inc DA, NE, and 5-HT neurotransmitters
- CNS crossing capability:
- Fast CNS penetration
- Produces immediate stimulation, euphoria –> higher potential for addiction/abuse
- Low dose effects vs. high dose effects
- Effects = dose related; tolerance develops
- Low dose = mental alertness, wakefulness, increased E
- High dose = psychoses and oral damage (“meth mouth”)
- Like cocaine, meth crosses placenta (found in breast milk)
Meth vs. Cocaine
- 1/2 life
- length of paranoia
Produce many similar acute and chronic effects i.e. mydriasis, euphoria, paranoia, psychosis, tachycardia, HTN, insomnia
- 1/2 life
- Cocaine: 1-2 hrs
- Meth: 8-12 hrs
- length of paranoia
- Cocaine: 4-8 hrs following drug cessation
- Meth: 7-14 days
- Meth psychosis may require meds/hospitalization –> may be irreversible
Overdosing can cause severe convulsions followed by CV and respiratory collapse, coma, and death (more with meth OD).
Other abused stimulants (3)
- GNB (gamma hydroxybutyric acid), “date rape” drug - NOT an amphetamine
- MDMA (“Ecstasy”), derivative of methamphetamine
- “Bath Salts”, amphetamine-like stimulant designer drugs (look like epsom salts)
Meth:
Treatment of Addiction
Treatment of Withdrawal
Treatment of Addiction:
- No approved, safe and effective treatment for meth addiction.
- Best treatment of cocaine or meth addiction = PREVENTION
- Next best treatment: CBT
Treatment of Withdrawal
- Withdrawal effects similar to cocaine, but longer duration
- alpha 1 adrenergic antagonists (prazosin) to relieve withdrawal symptoms
- Antipsychotics
- Anxiolytics
- Antidepressants
