How does dopamine affect the body differently at high versus low doses?
High: increases TPR (via alpha rec) and stimulates heart (via beta rec)
Low: Vasodilate kidney, mesentery, brain and heart
How do the D1 and D2 dopamine receptors differ?
D1: enhances adenylate cyclase activity, making more cAMP and causing nerve depolarization
D2: inhibits adenylate cyclase activity, making less cAMP and more IP3 and DAG, causing hyperpolarization
What are the common symptoms and histological signs of Parkinson's Disease?
Symptoms: bradykinesia, muscle rigidity, resting tremor, postural imbalance
Signs: Lewy Bodies and progressive loss of the melanin-pigmented dopaminergic neurons of the substantia nigra
What is the method of action of L-DOPA?
It is meant to supplement the lost DA from neronal death. It has a short half life but is uptaken into the striatal nerve terminals for sustained use.
Why are Carbidopa and Benserazide often given with L-DOPA?
They help to allow more LDOPA to enter the CNS, and decrease nausea side effects.
How do Dopamine receptor agonists differ from L-DOPA?
They have a longer duration and dont' rely on surviving DA nerve terminals, and thus no on/off effect occurs over time. New ones are D2 selective.
What is the method of action for Selegiline?
Irreversible MAO-B inhibitor (only in striatum). It causes no wine/beer/cheese effect, and protects striatal dopamine from MAO breakdown.
How do COMT inhibitors work?
They increase the amount of dopamine available to the brain.
How are muscarinic AchR antagonists often used in the context of Parkinson's?
In conjunction with L-DOPA.
How does Amantidine work for Parkinson's?
It increases dopamine release from striatal terminus. Often used with L-DOPA.
How does drug-induced Parkinson's come about, and which populations it the biggest issue for?
It arises from a decrease in DA in nerve terminals.
Elderly populations taking Reserpine often encounter it.
It is a side effect of classical antipsychotics (problem for Schizophrenic patients) because it knocks out D2 receptors.