Pharm- 13 Flashcards
Which enzyme converts Tyr –> L-DOPA?
Tyrosine hydroxylase
Which AA makes dopamine?
Tyr
What is special about tyosine hydroxylase as far as the synthesis steps?
Its the rate-limiting step
What 2 substrates does tyrosine hydroxylase use to make L-DOPA from Tyr?
BH4 and O2
What enzyme converts L-DOPA –> Dopamine?
dopamine decarboxylase
What cofactor does dopa decarboxylase need?
PLP
Define: used to move a majority of DA back into the presynaptic cell; it’s a 12 transmembrane domain protein belongs to a family of catecholamine reuptake pumps
Dopamine Transporter (DAT)
True or false: Dopamine uses secondary active transport to get into the presynaptic cell.
True
What molecules does DA enter with into the cell throguh DAT?
Na+ and Cl-. (Na is the 1 that is made from the secondary active transport usign the Na/K ATPAase)
What transporter puts DA back into the synaptic vesicle?
VMAT
What 2 enzymes break down DA in the persynaptic terminal cytosol?
MAO and COMT
Which form of MAO (MAO-A or MAO-B) can degrade DA?
TRICK QUESTION LOL. Both can degrade DA.
Where is MAO-A expressed, brain or periphery?
GOT U AGAIN. ITS BOTH AHAHAHAHA
Where is MAO-B expressed, brain or periphery?
Just the brain.
So MAO-B inhibitors inhibit the breakdown of dopamine where?
CNS
What weird molecule in wine and cheese increases if you’re taking an MAOi?
Tyramine
Where is COMT expressed?
Brain, heart, liver and kidneys
The breakdown of DA from COMT and MAO’s break it down into which molecule?
HVA
Where can you test HVA to see the rate of DA breakdown?
Pee pee
D1- metabotropic or ionotropic
metabotropic
D1- Gs, Gq, or Gi?
Gs
D2- metabotropic or ionotropic?
metabotropic
D2- Gs, Gq, or Gi?
Gi
Which dopamine receptors are in the striatum (caudate and putamen)?
D1 and D2 (remember parkinsons???)
Which dopamine receptors are in the basal ganglia?
D1 and D2
Which dopamine receptors are in the substantia nigra?
D2 and D4
Which dopamine receptors are in the nucleus accumbens?
D1, D2, D3 (help with movement)
Which dopamine receptors are in the olfactory tubercle?
D1, D2, D3, D5
Which dopamine receptors are in the lactotrophs?
D2 (regulate prolactin secretion)
Where is the area postrema?
located in the floor of the fourth ventricle is also a target of dopamine therapies
What happens if you stimualte the area postrema?
VOMITING. It’s a circumventricular organ.
Which R’s can you block in the area postrema to stop nausea and vomiting?
D2
What area of the brain is lost in parkinsons?
Substantia nigra pars compacta
Approximately what % of neurons are lost in parkinsons before Sx appear?
70%
What % of neurons are lost in the SNpc at autopsy?
95%
What are the Sx to parkinsons?
Bradykinesia or slowness of movement
Rigidity and resistance to passive movement of the limbs
Impaired postural balance which predispose to falling
Characteristic tremor when limbs at rest pill rolling
Stone like facial expression and drooling
What drug(s) can you give to treat parkinsons?
A. Dopamine B. Dopamine + Carbidopa C. Poop D. L-DOPA + Carbidopa E. Ach + Carbidopa
D. L-DOPA + carbidopa
Why can’t you use DA to treat parkinsons?
it doesnt cross the BBB
What is the fxn of carbidopa?
Doesnt allow the breakdown of L-DOPA in the periphery
Does carbidopa cross the BBB?
NO
What is levodopa used for?
Parkinsons
What are the adverse effects with levodopa?
skinesia, heart disease, orthostatic hypoTN, psychosis, loss of appetite, nausea, vomiting.
What must you give levodopa with?
Carbidopa
What class is levodopa for treating parkinsons?
dopamine precursor
What class is pramipexole and ropinerole?
Dopamine receptor agonists (D3 mainly)
What is pramipexole used for?
parkinsons
What is ropinerole used for?
Restless leg syndrome
What are the side effects to pramipexole and ropinirole?
dyskinesia, orthostatic hypoTN, weird CNS crap
What class of drugs is rasagiline or selegiline to treat parkinsons?
inhibit dopamine breakdown in the CNS (inhibit COMT or MAO)
What are the adverse effects to rasagiline or selegiline?
bundle branch block, GIII hemorrhage, dyskinesia, orthostatic hypoTN
