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35 Cards in this Set
- Front
- Back
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Dopamine is an inhibitory factor for
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prolactin
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Drugs which increase DA release in the _____ are generally reinforcing agents
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Nucleus Accumbens
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What is the mechanism of action for cocaine?
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Binds all 3 biogenic amine transportors (5HT, NE, DA)
Binds to DAT and inhibits the reuptake is the reinforcing addictive property |
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What is tolerance like for cocaine?
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Very low (especially compared to enormous tolerance for opiates)
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Is there a physical withdrawl from cocaine?
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No, dont get the same sympathetic withdrawal like alcohol
however, most powerful psychological reinforcing/addicting drug |
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What type of toxicity is associated with cocaine
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Sympathomemetic, too much NE in the periphery, increased BP and HR along with psychosis
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In addition to removing DA from the nigral striatal system in Parkinson's what other abnormality is seen with neurotransmitters?
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Since you lost inhibitory action of DA, acetylcholine revs up and there is increased cholinergic activity
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What does an increased DA to Ach ratio in the nigral striatal pathway cause
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Dyskinesias like Tardive Dyskinesia, Chorea
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What is the enzyme responsible for dopamine synthesis
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Aromatic amino acid decarboxylase
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If there is too much DA in the periphery it could get converted to
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Norepinephrine and then Epinephrine, which cause sympathomimetic effects
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Describe features and action of Carbidopa
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An AAAD inhibitor
Does not cross blood/brain barrier Irreversibly inhibits peripheral AAAD Decreases the effective dose of L-DOPA |
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Name 5 side effects of L DOPA
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On/Off syndrome
Nausea and vommitting Cardiac stimulation Loss of efficacy due to neuronal degeneration Psychosis |
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Why is nausea a side effect of L-Dopa?
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The increase in DA in the entire brain can trigger activity in a zone where DA stimulation causes nausea and vomiting
Patients can gain tolerance to this |
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What is bromocryptine
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A direct agonist of DA receptor but produces LOTS of side effects especially inhibition of prolactin
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Describe action and use of Deprenyl
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MAO inhibiotr, can be used as alternative to L-dopa
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What is amantadine and can it be used in Parkinson's?
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It's originally an antiviral, not sure of mechanism but increases DA release
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What drug is commonly used in Parkinson's to decrease Ach?
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Benztropine, a muscarinic antagonist, lots of side effects
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Name 4 factors that can cause Parkinsons symptoms
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Slow viruses (encephalitis)
Heavy metal poisoning MPTP Anti psychotics |
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What does MPTP do to cause Parkinson's symptoms?
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It was a contaminent in designer drugs of 70s, can destroy DA terminals.
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Which drugs are in the class of phenothiazines
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Chloropromazine- Aliphatic chain (one of first sedatives)
Thioridazine - piperdine side chain Piperazine- trifluoperazine chain |
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Name a butyrophenone that is extremely potent (also, which phenothiazine is just as potent)
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Haloperidol is a butyrophenone
Piperazine just as potent |
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How do typical neuroleptics (phenothiazines and butyrophenones work)?
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They are antagonists at D2 receptor
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How does clozapine work?
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It is an atypical antipsychotic, binds weakly at D2 receptor and very potently at D4
Serious side effects of agranulocytosis |
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How does olazapine work?
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It's an aypical antipsychotic similar to clozapine but safer, works at D2 weakly and D4 strongly
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How does risperidone work?
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It is an aytpical antipsychotic that antagonizes D2, 5-HT2, alpha-adrenergic, and histamine
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Classic neuroleptics block behavorial actions of
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dopamine agonists, they are D2 antagonists
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More potent drugs have a lower or higher Kd value?
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More potent the drug the lower the Kd value
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What is a therapeutic consequence of dopamine receptor antagonists in terms of neuron homeostasis?
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By blocking post and presynaptic receptors, the neuron can no longer regulate itself (DA binding to presynaptic inhibits DA release) now you have increased DA synthesis and release
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Explain the Dopamine theory of schizophrenia
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Schizophrenia is produced by hyper-function of CNS dopamine system
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What evidence supports the dopamine theory of schizophrenia
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Neuroleptics work at treating and are D2 antagonists
L-dopa can cause psychotic symptoms Amphetamine psychosis mimics schizophrenia and is treated w neuroleptics |
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What receptor are neuroleptics working at to produce the side effect of sedation
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Alpha 1 adrenergic antagonist
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What receptor are neuroleptics working at to produce the side effect of orthostatic hypotension
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Alpha 1 adrenergic antagonists
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Chronic side effects of Neuroleptics
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Tardive dyskinesia, hypermobility
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Why does thioridazine produce less side effects than other neuroleptics?
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By coincidence it has affinity at the muscarinic receptor, helps restore the DA/ Ach proper ratio
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If you want lower sedation use
If you want lower Parkinsons use- |
Sedation lower- use potent drugs piperazine and butyrophenone
Parkinsons symptoms lower- use less potent thioridazine |
