More CNS Drugs

  1. Naltrexone
    uses and mechanism
    Opioid antagonist

    blocks most of the rewarding effects of ethanol

    dont use with disulfiram since both are toxic to liver
  2. Baclofen
    high affinity GABA b receptor agonist

    reduce drug craving
  3. Modafinil
    combine with behavioral therapy may help treat cocaine addiction
  4. Clonidine
    since withdrawal symptoms relate to increased sympathetic activity, it can be useful in reducing them...

    a2 agonist
  5. sizzurp
    codeine/promethazine cough syrup 

  6. pancakes and syrup
    codeine/promethazine cough syrup

  7. Drugs that bind to biogenic amine transporters
    • Cocaine
    • Amphetamine
    • MDMA
  8. Drugs that bind to ion channels
    • Nicotine
    • Alcohol
    • BDZ's
    • Phencyclidine
  9. Drugs that activate G protein coupled receptors
    • Opiods
    • Cannabinoids
    • LSD
    • GHB
  10. Common prescription CNS stimulants
    • Methylphenidate (Ritalin)
    • Dextroamphetamine (Adderall)
    • Dexmethylphenidate (focalin)
  11. Mephedrone
    synthetic stimulant marketed via the internet from the far east... highly addictive and untested
  12. Psychostimulant effects
    • elevated mood
    • euphoria
    • alertness
    • reduced fatigue
    • increased energy
    • decreased appetite
    • relief of boredom
    • increased motor activity
    • increased heart rate
    • increased blood pressure
  13. Cocaine

    routes of admin, 3 actions, half life and metabolism
    most frequent illicit drug in ED visits

    • local anesthetic properties
    • vasoconstriction
    • psychostimulant

    • oral, intranasal, IV and inhalation
    • oral: absorption over an hour; 75% first pass
    • intranasal: vasoconstriction limits absorption
    • inhalation: rapid and complete absorption... onset in seconds and only persist 5-10 minutes
    • IV: bypasses all barriers to absorption... immediate action

    Half life: 50-90 minutes... metabolized by plasma and liver esterases and P450

    • metabolites are toxic to liver... 
    • benzoylecgonine indicates drug accumulation for long term users
  14. Cocaine
    directly blocks voltage gated sodium channels

    blocks reuptake of DA, NE, 5HT

    vasoconstriction due to inhibition of NE

    increased dopaminergic activity in mesolimbic pathway
  15. Acute effects of Cocaine
    euphoria, insomnia, irritability

    tachycardia, vasoconstriction, hypertension, bronchodilation, mydriasis

    giddiness, cognition change, hunger, sex, thirst

    loss of coordination, tremors, seizures followed by depression dysphoria anxiety and drug craving

    Arrhythmias are also a problem
  16. Chronic effects of cocaine
    psychotic behavior (toxic paranoid psychosis)

    suppressed appetite, delayed sleep and restlessness

    nasal septal necrosis from snorting

    sexual dysfunction, depressive conditions and violent behavior
  17. The RUNS
    drug taking, craving, drug taking, craving, drug taking

    until the patient crashes... 

    they do this to prevent the crash from happening

    leads to the crash and then sleep and "the blues" and then will start over again
  18. Cocaine Overdose
    • excessive activation of the sympathetic nervous system... tachycardia and hypertension, coronary vasoconstriction
    • MI or cerebrovascular hemorrhage

    coronary vasospasms and arrhythmias

    rapidly fatal dying within minutes
  19. Treatment of Cocaine OD
    sedatives (diazepam) to stop hyperactivity and psychosis

    b1 blockers (atenolol) to stop sympathetic effects on heart

    nitroglycerine for angina

    calcium channel blockers for hypertension (verapamil, diltiazem)

    supportive therapy for other symptoms
  20. Cocaine in pregnancy
    • crack babies...
    • infants may suffer growth retardation, microcephaly and brain problems

    likely risk for developmental and behavioral problems during childhool
  21. Amphetamines
    increases the concentration of dopamine in the synaptic cleft in four ways:

    • 1. binds to presynaptic membrane and induces release of DA
    • 2. interacts with VMAT releasing free dopamine into terminal
    • 3. inhibits MAO-A and B
    • 4. reverses the DAT reuptake transporter and causes DA transport out of the cell
  22. Amphetamines 
    metabolism and elimination
    • metabolism via CYP2D6
    • deamination - inactivate
    • oxidation - activate
    • parahydroxylation - active

    eliminated in urine... increased by lowering pH
  23. Acute Amphetamine effects
    • CNS
    • euphoria (low dose)
    •   increase energy and alertness
    •   increase sociability
    •   decrease appetite
    • Dysphoria (high dose)
    •   panic attacks and anxiety
    •   irritability
    •   suspicious
    •   psychosis
    •   seizures
    •   movement disorders

    • CV
    • increase Bp (reflex brady)
    • coronary vasoconstriction
    • AMI, ischemia
    • stroke

    • Pulmonary
    • bronchodilation
    • bronchospasm
    • P Edema
  24. Acute amphetamine effects
    • low doses
    • increase MAP and brady, coronary vasoconstriction, bronchodilation

    • moderate doses
    • stimulate respiration, tremors, restlessness, insomnia, agitation, appetite suppression, sleep deprivation

    • high doses
    • continual purposeless acts, aggression and violence, paranoid delusions, anorexia and amphetamine psychosis (indistinguishable from acute schizophrenia)
  25. Chronic Amphetamine Effects
    similar to cocaine

    paranoid psychosis

    amphetamine-specific arteritis small and medium sized arteries... fatal brain hemorrhage or renal failure
  26. Medical uses of amphetamines
    • narcolepsy
    • ADHD
    • obesity (appetite suppression)
  27. Methamphetamine
    Crank, Crystal, Speed

    more potent than amphetamine

    when converted to base form (ICE) can be vaporized and inhaled

    ICE-induced psychosis can last a few days to a week
  28. MDMA, Ecstasy

    stimulant, pseudo-hallucinogen, empathogen

    release of biogenic amines by reversing the serotonin transporter

    inhibition of tryptophan hydroxylase, MAO A/B inhibition

    also inhibits CYP2D6 (impairs own metabolism)
  29. MDMA, Ecstasy 
    hyperthermia, leading to dehydration and multi-organ failure

    in overdose, causes increased heart rate and decreased contractility and unconsciousness and seizures

    • distorts time and perceptions
    • enhanced empathy and communication

    possibly neurotoxicity b/c of permanent damage to serotonin neurons
  30. Nicotine
    • highly lipophillic
    • half life 30 minutes
    • metabolized by CYP2A6

    increases sympathetic and parasympathetics

    depolarization of thermo, mechano, and nociceptors in periphery

    stimulates release of dopamine in mesolimbic (addictive behavior)

    biphasic stimulation of nicotinic receptors in brain and periphery
  31. withdrawal symptoms of nicotine
    nervousness, anxiety, drowsiness, disturbed sleep, lightheadedness, insomnia, dizziness, tremor, decreased concentration, and intense craving for tobacco
  32. Nicotine dependence treatment
    nicotine patch or gum

    antidepressant bupropion is useful

    varenicline is a selective nicotine receptor partial agonist
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More CNS Drugs
dr. pedigo's CNS section