1. Insulation of axons
    • CNS= oligodendrocytes
    • PNS= Schwaan cells
  2. What does tetrodotoxin do?
    Inhibits sodium voltage gated channels (inhibits saltatory conduction)-> Death
  3. What do Ouabain and digitalis do?
    Inhibit sodium/K Atpase
  4. Similarities between NMDA and GABA receptors
    • a) ligand bindingn site (NT)
    • B) channel binding side (regulators, poisons)
    • c) modifiers/co-activator site

    Differences: NMDA lets in calcium, GABA lets in chlorine
  5. What enzyme turns Glutamate into GABA
    Glutamate decaboxylase
  6. actions of Methylxanthines
    • Inhibits PDE-> Increases cAMP
    • increase intracellular calcium (cardiac contractility)
    • blocks adenosine receptors
    • inhibits prostaglandins
    • stimulates gastric acid secretion
  7. metabolism of methylxanthines
    metabolized by liver cyps

    OH-hydroxylations and demethylation
  8. actions of nicotine
    • Stimlates sympathetic ganglia/adrenal medulla
    • increaased BP, heart rate, vasoconstriction

    Sympathetic<parasympathetic<parasympathetic blockade

    major metabolite= cotinine, N'-oxide
  9. Actions of Cocaine
    • Stimulation of cortex and brain stem
    • blocks presynaptic reuptake of NE, serotonin and DA by blocking DAT

    Sympathetic potentiator (vasoconstriction, tachycardia etc. )

    Local anesthetic by inhibition of voltage-dependent Na channels
  10. What do imipramine and amitriptyline do?
    Synthetic drugs that inhibit DAT
  11. MOA: Amphetamines
    • NT elevated through increased release from intracellular stores
    • inhibition of monamine oxidase

    structurally most similar to NE and 5-ht (some convergence with DA), thus mostly noradrenergic effects

    Hallucinations largely auditory and tactile in nature with a strong paranoia component
  12. What's special about methamphetamine
    higher ratio of CNS:PNS effects
  13. moa of LSD
    • Serotonin agonist  (note that serotonin is derived from tryptophan, and LSD looks like tryptophan/5-ht) @ midbrain-presynaptic membrane
    • activation of sympathetic neurons 

    • visual hallucinations
    • high potency
  14. What can you use haloperidol for?
    Blocks LSD effects
  15. MOA of phencyclidine
    Blockade of NMDA by PCP induces/exacerbates psychotic symptom

    Partial agonist at Dopamine D2 receptors
  16. NMDA receptors
    Usually have a magnesium block, glutamate binds MG2+ allowing calcium to enter, increasing depolarization

    PCP binds an adjacent site on NMDA, blocking the receptor from activation, thus downstream neurons have greater Dopamine activity
  17. MOA of benzodiazepines
    • Binds GABAa receptor subtype at a co-activator site, crowding the normal conformation of the receptors, causing excessive opening of chloride channels when GABA binds
    • reduces anxiety by selectively inhibiting limbic circuits
    • no anti-psychotic effects
    • sedative properties, hypnotic at higher levels
    • anti-convulsant
    • muscle relaxant-> presynaptic inhibition on spinal cord

    highest density of binding sites in cerebral cortex, amygdala, hippocampus, hypothalamus
  18. What is flumazenil used for?
    Anaonist for diazepam
  19. Tricyclic anti-depressants
    MOA: blocks reuptake of neurotransmitters DA, NE, 5-HT; take time to exhibit effects possibly due to cellular changes. Also inhibit a-adrenergic, histamine, muscarinic receptors

    • don't exhibit their anti-depressive effects in normal individuals. 
    • mood elevation slow in onset, but effects are persistent. 
    • tolerance to anti-cholinergic adverse events and autonomic effects develops. 
    • strong component of psychological and physical dependence.
  20. TCAs and their effects on various other drugs
    • TCA+ethanol: toxic sedation
    • TCA+ indirect sympathetics: blocks effects by preventing indirect mimmetic from getting to their intracellular site of action
    • TCA+ direct sympathetics: potentiates the effects
    • TCA+MAO-I: potentiation, can cause hypertensive crisis.
  21. Cannabis
    • Delta 9 Tetrahydrocannabinol most potent cannabinoid
    • THC binds to GPCR (CB1=CNS, CB2=PNS)
    • CB1 activation=pleasure perception and reward

    Oxidized to inactive THC-COOH in the liver, reation p450 mediated
  22. Cerebral Ischemia
    • subtype of stroke, characterized by decrease in cerebral blood flow to brian tissue (87% of all strokes)
    • Focal ischemia: CBF reduced at specific region of the brain
    • Global ischemia: CBF reduced at most parts of the brain

    ATP decrease due to lack of CBF leads  to excessive influx of Ca2+, and activation of apoptosis. Involves: elevated calcium activated lipases, kinases, endonucleases, and ROS

    t-PA is an effective current treatment
  23. Lithium treatment
    • decreases severity and frequency of manic episodes in bipolar disorders. 
    • Lithium carbonate mostly prescribed
    • Lithium modulates activity of NT(primarily glutamate) to protect neurons from excitotoxicity. Lithium inhibits GSK3 and IP3

    • Lithium decreases brain inflammation
    • Lithium is absorbed in GI tract, well distributed, and excreted in urine. 

    Lithium has a number of adverse effects, thus concentrations should be regularly monitored
  24. Alzheimer's disease
    Amyloid B hypothesis: Abnormal elevation or insufficent clearance of AB oligomers may underlie AD pathology. AB oligomers thought to be more injurious than AB-plaques

    AB Oligomers diffuse into synaptic cleft and disrupt signal transmission. Oligomers will eventually aggregate forming plaques

    Tau hypothesis: aggregates of hyperphosphorylated tau protein form NFT. Amyloid B is thought to promote phosphorylation of Tau. 

    Mitochondrial hypothesis: APP induces mitochondrial dysfunction in neuronal cells

    • Treatments: 
    • Donepezil= cholinesterase inhibitor to increase Ach levels
    • Memantine= prevent glutamate reuptake by nerve cells
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