Term
| What are the four pathways were we see dopamine? Where are they running and what do they do? |
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Definition
1. **Nigrostriatal tract; from substantia nigra to the striatum [MOVEMENT]
-Loss of DA neurons here leads to the excess action of ACh on GABA-ergic neurons and extrapyramidal dysfunction seen in Parkinson Disease
-Antagonists-->pseudo-Parkinsonism
-Agonist-->(hypokinetic) dyskinesias
2. Mesolimbic-mesocortical tracts; in midbrain and projects to frontal cortex and limbic structures [MOOD]
-Agonist-->pleasure and desire to repeat (reinforcement); drug addiction and psychosis (the repetitive behaviors of)
-Also deals with perception of sensory stimuli & affect
-Antagonists-->decreased cognitive function
3. Tuberoinfundibular tract; cell bodies from hypothalamus to the anterior pituitary to lower *prolactin (milk secretion)
-Agonists-->for hyperprolactinemic states (pit. tumor)
-Antagonists-->cause endocrine dysfunction (gynecomastia or milk production)
-Also inhibits GH (acromegaly without), regulates temp. (get hot without), and inhibits appetite (get fat without)
4. Chemoreceptor trigger zone; vomiting
-Common side effect & can antagonize for chemo patients |
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Term
| What are the types of dopamine receptors? What are the two most important ones? |
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Definition
-D1 & D2 types
-D2a; nigrostriatal-->movement
-D2c; mesolimbic--> mood (better target for antipsychotics-->Clozapine; but rest are non selective) |
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Term
| What is Parkinson disease? When do we see it? What are the symptoms? |
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Definition
-In about 2% of the pop. over 70; from oxidative injury to dopamine neurons in *nigrostriatum (non-familial)
Pathology;
-Too little DA and too much ACh
**Triad of symptoms;
-Bradykinesia; slow onset of movement, gives shuffling
-Muscle rigidity
-Resting tremor |
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Term
| What are four strategies we could use for Parkinson's? |
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Definition
1. L-DOPA-->increases DA synth
2. DA receptor agonist
3. M receptor antagonist (atropine and others)
4. Selegiline-->inhibits MAO-B
-Reference page 161 |
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Term
| What is levodopa? What is it given with? Side effects? |
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Definition
-It is taken up in the brain and converted to dopamine
-**Carbidopa is given with it and inhibits *peripheral metabolism by AAAD (aromatic amino acid decarboxylase); converts L-dopa to dopamine
-Carbidopa doesn't cross BBB (need conversion in CNS)
Side effects;
-Dyskinesias with "on-off" effects; from fluctuations
-Psychosis; from mesolimbic/cortical tracts
-Vomiting; from chemoreceptor trigger zone
-HypOtension; from periphery action in ANS
-Maybe some weight loss as well |
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Term
| How do we inhibit COMT? What does it do? |
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Definition
-Tolcapone and entacapone (-capones; Al Capone gets comped everywhere he goes lol)
-Tolcapone is hepatotoxic
-Crosses BBB (must inhibit there and periph)
-COMT converts DA and L-dopa to 3-O-methyldopa in the periphery *and in the CNS; acts as partial agonist
-D receptors are blocked, and uptake is lowered |
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Term
| How do we inhibit MAOb? What does it do? Side effects |
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Definition
-*Selegiline
-It is very **selective for MAOb so we see no tyramine interactions (MAOa inh. + tyramine [releaser] gives *hypertensive crisis)
-MAOb metabolizes DA in the neurons
-Still get dyskinesias and psychosis (from two main tracts)
-Also get *insomnia b/c selegeline is metabolized to *amphetamine (a psychostimulant)
-Think of a cat named Geline who's on amphetamine and goes MAOoOoOoOO!... so we want to sell her haha. |
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Term
| What are some dopamine-receptor agonist? What do they treat? |
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Definition
*Bromocriptine & pergolide
-For hyperprolactinemia and acromegaly (both from tuberoinfundibular tract)
-*Dyskinesias and psychosis* is too much with direct antagonism for Parkinson's use
*Pramipexole & *ropinirole
-Can be used for Parkinson's and are also *antioxidants
-BP PR |
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Term
| What are the antimuscarinics we use for Parkinson disease? Side effects? |
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Definition
-Benztropine & trihexyphenidyl; already learned (atropine-like)
-*Diphenhydramine; an antihistamine (**all antihistamines are potent anti-muscarinic drugs)
-Often for acute attacks (from over blockage of DA when treating psychosis)
Side effects; (All M block related)
-Dry mouth (low secretions)
-Blurred vision (no accommodation)
-Mydriasis (SANS takes over)-->glaucoma maybe
-Urinary and fecal retention
-Three Cs (cardiotoxicity, convulsions, coma) |
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Term
| What is amantadine? Side effect? |
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Definition
Antiviral medication that also;
-Is an *M-blocker
-*Increases dopamine release
Side effects;
-Atropine-like
-***Livedo reticularis (only one that will do this); swollen venules that gives reddish-purple spiderweb appearance |
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Term
| What is the theory and treatment strategy for psychosis? |
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Definition
-↑DA→positive symptoms (hallucinations, delusions, etc.)
-↓5HT→negative symptoms (social withdraw, etc.)
-Came up with this because DA agonist can cause psychosis, and antagonist can treat psychosis
-Strategy then is **block DA and **↑5HT (with **5HT2 receptors**; do neg. feedback similar to α2) |
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Term
| What is the difference b/t typical and atypical antipsychotics? |
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Definition
-Typical antagonize DA receptors
-Atypical do other things |
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Term
| What is the special DA blocker for Tourette syndrome? |
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Definition
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Term
| What do we expect as side effects to antipsychotics? |
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Definition
DA blockade;
1. Dyskinesias (called extrapyramidal symptoms; **EPS)
-Progresses from acute to chronic (**Tardive dyskinesia)
-Treat initially with anti-Ms, but chronic is irreversible
2. Dysphoria (disruption of reward pathway)
3. Endocrine dysfunction (*temp, prolactin, & eating)
Muscarinic blockade; tachycardia and ↓seizure threshold
Alpha blockade; hypotension (w/ reflex tachy)
-These two are just accidental blockades
-Check **163 for full info (esp. for EPSs) |
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Term
| Specifically, what is the temp problem associated with DA blockade and how do we treat? Drug most likely to cause? |
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Definition
-**Neuroleptic malignant syndrome (NMS); very similar to malignant hyperthermia caused by succinylcholine (depolarizing muscle relaxant)
-Treatment; Bromocriptine (DA agonist) and dantrolene (blocks Ca2+ channels in SR)
-Haloperidol or fluphenazine are most likely (little M-blocking activity) |
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Term
| What is the main advantage to the atypical drugs? What is a strange effect of 5HT2 antagonism? |
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Definition
-Less EPS
-Wet pillow syndrome (increased salvation) |
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Term
| Go through the drug list on pg. 164. |
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Definition
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