Dopaminergic Pharmacology and Parkinsons Disease

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courtney3672
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62944
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Dopaminergic Pharmacology and Parkinsons Disease
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2011-01-30 18:39:07
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Dopaminergic Pharmacology Parkinsons Disease
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Systems Pharmacology
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  1. What is the enzyme responsible for the conversion of tyrosine into L-Dopa?
    Tyrosine Hydroxylase

  2. Dopamine is converted to norepinephine by what enzyme?
    Dopamine Beta hydroxylase

  3. L-Dopa is converted to dopamine by what enzyme?
    DDC- dopamine decarboxylase
  4. What is the major metabolite of DA catabolism?
    HVA: homovanillic acid
  5. Would lower levels of HVA indicate an increase or decrease in DA activity?
    lower HVA indicates lower DA activity.
  6. DA is broken down into its major metabolite by what two enzymes?
    • COMT- catechol-O-methyl transferase
    • and
    • MAO- monoamine oxidases

  7. What two enzymes are responsible for the breakdown of DA? What is the name of DA's major metabolite?
    • MAO
    • COMT
    • HVA
  8. What is the major dopaminergic system in the brain?
    NIGROSTRIATAL - FROM THE SUBSTANTIA NIGRA (cell bodies) TO THE STRIATUM (terminals).
  9. What system/ circuit contains 80% of the brain's dopamine content?
    nigrostriatal system
  10. What are the secondary (not major) dopaminergice systems in the brain?
    Mesolimbic, Mesocortical, hypothalamic

    • Mesolimbic: From midbrain area A10 (“A-Ten”, or VTA) to nucleus
    • accumbens

    Mesocortical: From midbrain area A10 (“A-Ten”, or VTA) to frontal cortex

    Hypothalamic: From arcuate nucleaus to median eminence and pituitary.
  11. NE and DA have similar biosynthesis and vesicular uptake.... True or False
    True
  12. NE and DA use the same reuptake pumps...True or False
    False
  13. What drug inhibits tyrosine hydroxylase in both NE and DA neurons?
    AMT: alpha methyl tyrosine
  14. What drug inhibits vesicular uptake of both NE and DA?
    Reserpine
  15. Do amphetamines cause an increase in release in DA, NE, or both types of neurons?
    Both
  16. What drug of abuse inhibits reuptake at the nerve terminal in both DA and NE neurons?
    Cocaine
  17. Would desipramine inhibit neuronal reuptake of NE, DA, or both?
    Desipramine inhibits reuptake of NE but not DA
  18. Post-synaptic receptors for NE and DA have similar affinity for NE and DA agonists and antagonists.... True or False
    False
  19. Is reuptake or catabolism the major mechanism for ending the action of NE and DA?
    • Reuptake (not catabolism) of
    • transmitter is the major
    • mechanism for ending the action of
    • NE or DA.
  20. Will inhibiting DA or NE reuptake enhance or decrease DA or NE action at targets?
    Inhibiting DA or NE reuptake will enhance DA or NE action at targets because there will be more neurotransmitter in the cleft.
  21. What is the target of cocaine in the CNS?
    COCAINE – TARGETS CNS - A dopamine reuptake pump, probably in “reward centers” of the nucleus accumbens. Psychotropic.
  22. What is the target of cocaine in the peripheral nervous system?
    Periphery – Norepinephrine reuptake pumps in cardiovascular system.

    Increases Heart Rate, Vasoconstriction, and BP
  23. What is bradykinesia?
    Bradykinesia is is characterized by slowness of movement and has been linked to Parkinson's disease and other disorders of the basal ganglia. Rather than being a slowness in initiation (akinesia), bradykinesia describes a slowness in the execution of movement.
  24. What are the three major symptoms od Parkinsons Disease?
    • Symptoms: Bradykinesia, resting
    • tremor, rigidity progressing to
    • akinesia, dementia. Incurable.
  25. Patients with Parkinson's Disease show
    substantial loss of cell bodies in the
    ______and degeneration of the ______.
    • substantia nigra pars compacta
    • nigrostriatal tract
  26. Why does L-Dopa cross the blood brain barrier while dopamine does not?
    L-Dopa crosses the BBB because it is an amino acid and its transport is facilitated by a transporter.
  27. How can you enhance dopaminergic output? (4 ways)
    • Enhance dopaminergic function by:
    • 1) Increase [DA] in nigrostriatal neurons (levodopa)

    • 2) DA receptor agonists (pergolide,
    • bromocriptine) (ropinirole, pramipexole)
    • 3) DA reuptake inhibitors (cocaine)

    4) Enhance DA release (amantidine)
  28. In addition to increasing dopaminergic function to treat PD, you can also increase cholinergic input by giving ___?
    • Reduce cholinergic function by:
    • 1) ACh receptor antagonists (certain
    • centrally-acting antimuscarinics; e.g.,
    • benztropine)
  29. Carbidopa inhibits what step in DA biosynthesis?
    Carbidopa inhibits the enzyme DDC from converting L-Dopa into DA
  30. Carbidopa is unable to cross the blood brain barrier..... True or False?
    True
  31. If a patient is given a DA precursor such as levodopa, what effect will this have in the CNS? PNS?
    levodopa will cause an increase in the production of DA in both the CNS and PNS. The overproduction of DA in the PNS may lead to undesirable side effects.
  32. A patient with Parkinson's Disease is given a DDC inhibitor such as carbidopa. What effects will this produce in the CNS? PNS?
    There will not be any change in the biosynthesis of DA in the brain as carbidopa can not cross the BBB. In the PNS, DA biosynthesis will decrease.
  33. A patient with Parkinson's Disease is given a DA receptor agonist. Will this patient see any improvement in PD symptoms?
    Yes. An agonist at the dopamine receptors will alleviate symtpoms.
  34. A patient with Parkinson's Disease is given a DA receptor antagonist. Will this patient see any improvement in PD symptoms?
    No, this patient will have worse symptoms
  35. A patient with Parkinson's Disease is given a MAOI or COMTI. Will this patient see any improvement in PD symptoms?
    • Yes.
    • MAOI will inhibit the breakdown of DA, increasing its availabilty.
  36. A patient with Parkinson's Disease is given a ACh receptor agonist. Will this patient see any improvement in PD symptoms?
    No. An increase in ACh will worsen the symptoms.
  37. A patient with Parkinson's Disease is given an ACh receptor antagonist. Will this patient see any improvement in PD symptoms?
    Yes. This will help to restore ACh/ DA balance.

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