CNS I:Drugs for Neurodegenerative DiseasesA.Understand the basic functions of norepinephrine, dopamine, serotonin, acetylcholine and GABA in the CNS.Norepinephrine: (catecholamine) Acts on Alpha 1,2, and beta 1. Suppresses neural excitability, acts on adrenergic receptors, vasoconstriction.Domapine: (catecholamine) Released in substia nigra to the striatum to balance ACH. At low doses, acts on dopamine only, at moderate dose – include Beta 1, at high - include alpha1. Can increase CO, tissue perfusion, and renal perfusion. Monitoring urine output is essential. Counter indicated in pts w/cardial issues. Can cause dysrhythmiasSerotonin: Acts in brain and spinal cord; Stimulates 5HT receptors; generally inhibitory and involved in mood, anxiety and sleep, levels of serotonin are elevated in schizophrenia. Acetylcholine: Activates preganglionic neurons in in sympathetic, parasympathetic, and somatic systems; activiates postglaglinoic in parasympathetic. Acts on Muscarinic and nicotinic receptors. Degraded by ACHease. GABA: amino acid, an inhibitory transmitter, affects controlled motor movement.B.Succinctly summarize the main antiparkinsonian mechanisms of action, pharmacokinetics, monitoring, side effects, use in pregnancy, cautions and contraindications. And discuss which drug classes are recommended for initiating therapy vs adjunct therapy.a.Levodopa & carbidopa$$Most effective, first line for severe symptoms. Levodopa: dopamine replacement. Highly absorbed and metabolized in liver and GI track. Levadopa is converted by decarboxylation to dopamine. Full response take several months. Long term does not work. Can have loss of effect that can be managed w/dose intervals. Food delays absorption, particularly high-protein food. Levadopa has ½ life 1-2 hrs, causing on-off phenomenon. Adverse effects: N/V; dyskinesia; CV; Psychosis. Second generation antipsychotics: clozapine and quetiapine most effective. FGAs block D-receptors.CNS: compulsiveness and binge eatings, insomnia, nightmares. Skin: melanomaWithdrawl from MAO inhibitors (phenelzine) 2 weeks prior to levodopa to avoid HTN crisis caused by enhanced catacholimine production..