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35 Cards in this Set

  • Front
  • Back
Dopamine is an inhibitory factor for
Drugs which increase DA release in the _____ are generally reinforcing agents
Nucleus Accumbens
What is the mechanism of action for cocaine?
Binds all 3 biogenic amine transportors (5HT, NE, DA)
Binds to DAT and inhibits the reuptake is the reinforcing addictive property
What is tolerance like for cocaine?
Very low (especially compared to enormous tolerance for opiates)
Is there a physical withdrawl from cocaine?
No, dont get the same sympathetic withdrawal like alcohol

however, most powerful psychological reinforcing/addicting drug
What type of toxicity is associated with cocaine
Sympathomemetic, too much NE in the periphery, increased BP and HR along with psychosis
In addition to removing DA from the nigral striatal system in Parkinson's what other abnormality is seen with neurotransmitters?
Since you lost inhibitory action of DA, acetylcholine revs up and there is increased cholinergic activity
What does an increased DA to Ach ratio in the nigral striatal pathway cause
Dyskinesias like Tardive Dyskinesia, Chorea
What is the enzyme responsible for dopamine synthesis
Aromatic amino acid decarboxylase
If there is too much DA in the periphery it could get converted to
Norepinephrine and then Epinephrine, which cause sympathomimetic effects
Describe features and action of Carbidopa
An AAAD inhibitor
Does not cross blood/brain barrier
Irreversibly inhibits peripheral AAAD
Decreases the effective dose of L-DOPA
Name 5 side effects of L DOPA
On/Off syndrome
Nausea and vommitting
Cardiac stimulation
Loss of efficacy due to neuronal degeneration
Why is nausea a side effect of L-Dopa?
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
What is bromocryptine
A direct agonist of DA receptor but produces LOTS of side effects especially inhibition of prolactin
Describe action and use of Deprenyl
MAO inhibiotr, can be used as alternative to L-dopa
What is amantadine and can it be used in Parkinson's?
It's originally an antiviral, not sure of mechanism but increases DA release
What drug is commonly used in Parkinson's to decrease Ach?
Benztropine, a muscarinic antagonist, lots of side effects
Name 4 factors that can cause Parkinsons symptoms
Slow viruses (encephalitis)
Heavy metal poisoning
Anti psychotics
What does MPTP do to cause Parkinson's symptoms?
It was a contaminent in designer drugs of 70s, can destroy DA terminals.
Which drugs are in the class of phenothiazines
Chloropromazine- Aliphatic chain (one of first sedatives)
Thioridazine - piperdine side chain
Piperazine- trifluoperazine chain
Name a butyrophenone that is extremely potent (also, which phenothiazine is just as potent)
Haloperidol is a butyrophenone
Piperazine just as potent
How do typical neuroleptics (phenothiazines and butyrophenones work)?
They are antagonists at D2 receptor
How does clozapine work?
It is an atypical antipsychotic, binds weakly at D2 receptor and very potently at D4
Serious side effects of agranulocytosis
How does olazapine work?
It's an aypical antipsychotic similar to clozapine but safer, works at D2 weakly and D4 strongly
How does risperidone work?
It is an aytpical antipsychotic that antagonizes D2, 5-HT2, alpha-adrenergic, and histamine
Classic neuroleptics block behavorial actions of
dopamine agonists, they are D2 antagonists
More potent drugs have a lower or higher Kd value?
More potent the drug the lower the Kd value
What is a therapeutic consequence of dopamine receptor antagonists in terms of neuron homeostasis?
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
Explain the Dopamine theory of schizophrenia
Schizophrenia is produced by hyper-function of CNS dopamine system
What evidence supports the dopamine theory of schizophrenia
Neuroleptics work at treating and are D2 antagonists
L-dopa can cause psychotic symptoms
Amphetamine psychosis mimics schizophrenia and is treated w neuroleptics
What receptor are neuroleptics working at to produce the side effect of sedation
Alpha 1 adrenergic antagonist
What receptor are neuroleptics working at to produce the side effect of orthostatic hypotension
Alpha 1 adrenergic antagonists
Chronic side effects of Neuroleptics
Tardive dyskinesia, hypermobility
Why does thioridazine produce less side effects than other neuroleptics?
By coincidence it has affinity at the muscarinic receptor, helps restore the DA/ Ach proper ratio
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