Pharm E2 - Dopamine

Front 1

Projections involved in Schizophrenia:

From the substantia nigra -> striatum.

Substrate for extrapyramidal symptoms (EPS), resulting from antipsychotic treatment -> Parkinsonian symptoms.

Back 1

Nigrostriatal Projection

Front 2

Projections involved in Schizophrenia:

From 1) the ventral tegmental area -> nucleus accumbens: too much DA -> positive symptoms.

2) the ventral tegmental area -> frontal cortex: too little DA -> negative symptoms

Back 2

Mesocorticolimbic projection

Front 3

Projections involved in Schizophrenia:

From arcuate nucleus of hypothalamus -> median eminance and pars intermedia of pituitary.

D2 block -> endocrinological side effects: ^PRL release -> gynecomastia in males.

Back 3

Tuberoinfundibular system

Front 4

Projections involved in Schizophrenia:

Cell bodies in motor nucleus of vagus, ill-defined target area, involved in eating behavior -> weight gain.

Back 4

Medullary-periventricular neurons

Front 5

Projections involved in Schizophrenia:

antiemetic properties (not a bad thing).

Back 5

Dopamine receptors in CTZ

Front 6

What is it and when does it occur:

Unable to move; muscle spasm; retrocollis, torticollis

Back 6

Acute dystonia

1-5 days

Anticholinergic antipark agents are given diagnostically & curative to re-establish balance.

Front 7

What is it and when does it occur:

Motor restlessness

Back 7

Akasthesia

5-60 days

Decrease dose or change drug.
Treat with Benztropine or propranolol

Front 8

What is it and when does it occur:

Bradykinesia, rigidity, tremor, mask facies, shuffling gait.

Back 8

Parkinsonism

5-30 days

Antiparkinsons agents.
Anticholinergic

Front 9

What is it and when does it occur:

Catatonia, stupor, fever, unstable blood pressure, myoglobinemia; may be fatal

Back 9

Neuroleptic Malignant Syndrome

Weeks (can persist after stopping)

STOP DRUG!
Treat with Bromocriptine or Dantrolene
(antiparkinsons and anticholinergics don't work)

Front 10

What is it and when does it occur:

Tremor around lips and mouth

Back 10

Perioral tremor (Rabbit syndrome)

Months or years
(can worsen with drug withdrawl)

Prevention is key!
DO NOT use ANTI-CHOLINERGIC!

Front 11

• M.O.A.: converted to DA in the periphery AND/OR gains access to the CNS via the LAT (L-amino acid transpoerter) -> serves as DA precursor in CNS -> converted to DA via L-AAD (L-aromatic acid decarboxylase).

Back 11

Levodopa

Front 12

• M.O.A.: cannot cross BBB; inhibits L-AAD in the periphery -> more L-DOPA in periphery to get into CNS via LAT.

Back 12

Carbidopa

Front 13

• M.O.A.: deals with compensatory increase in COMT with Carbidopa use; can cross BBB -> inhibits COMT in periphery and CNS -> more L-DOPA available in both places to be made into DA.

Can decrease on-off phenomenon b/c central DA metabolism blocked -> decreases doses needed of L-DOPA and Carbidopa.

Back 13

Tolcapone

Front 14

• M.O.A.: Antimuscarinic/ anticholinergic -> blocks the muscarinic receptor on the GABA efferent neuron -> Ach cannot bind -> decrease excitatory effect on GABA neuron -> improves pts movements.

Back 14

Benztropine

Front 15

• M.O.A.: acts at Nigrostriatal neuron terminal -> 1) inhibits reuptake of DA, and 2) promotes more DA release from terminal.

Back 15

Amantadine

Front 16

• M.O.A.: D2 agonist -> stimulates receptor directly -> decreases need for more DA altogether.

Allows decreased dose of L-DOPA

Decreased on-off phenomenon.

Can be used in pts becoming refractory to L-DOPA

Back 16

Bromocriptine (ergot)

Front 17

• M.O.A.: D2 agonist -> stimulates receptor directly -> decreases need for more DA altogether.

Allows decreased dose of L-DOPA

Decreases on-off phenomenon.

Can be used in pts becoming refractory to L-DOPA

Back 17

Ropinirole

Front 18

• M.O.A.: Selective MAO-B inhibitor -> prevents metabolism of DA in CNS -> decrease disease effects.

Allows a decrease in dose of L-DOPA needed.

Decreased on-off phenomenon.

Back 18

Selegiline

Front 19

• M.O.A.: D2 blocker in CNS and periphery -> Decreased DA acting on striatum -> decreased positive symptoms.

Back 19

Chlorpromazine: Phenothiazine/ thioxanthene

Front 20

• M.O.A.: D2 blocker in CNS and periphery -> decreases DA acting on striatum -> decrease positive symptoms.

Back 20

Haloperidol: Butyrophenone

Front 21

• M.O.A.:
Selective for causing DPI ONLY in mesolimbic pathway, not nigrostriatal pathway.

Decreases EPS b/c not so much block on nigrostriatal projection -> decreases negative symptoms.
 Higher potency at 5-HT2 receptors.

Back 21

Clozapine

Front 22

• M.O.A.:
Selective for causing DPI ONLY in mesolimbic pathway, not nigrostriatal pathway.

Decreased EPS b/c not so much block on nigrostriatal projection -> decreased negative symptoms.

Back 22

Risperidone

Front 23

• M.O.A.:

Selective for causing DPI ONLY in mesolimbic pathway, not nigrostriatal pathway.

Decreased EPS b/c not so much block on nigrostriatal projection -> decreased negative symptoms.

Back 23

Olanzapine

Front 24

• M.O.A.:

Selective for causing DPI ONLY in mesolimbic pathway, not nigrostriatal pathway.

Decreased EPS b/c not so much block on nigrostriatal projection -> decreaed negative symptoms.

Back 24

Ziprasodone

Front 25

• M.O.A.:

Partial agonist at D2 receptors -> increased DA activity at frontal cortex AND decreased DA activity at VTA.

Modest affinity at 5-HT2 receptors; partial agonist there.

Back 25

Aripiprazole (Abilify)