T42 drugs for neurogenerative diseases

alzheimer's & parkinson's

alzheimer’s disease - effects what areas of brain

hippocampus, cerebral cortex

alzheimer’s disease - pathological hallmarks

accumulation of amyloid plaque (amyloid β peptide), neurofibrillary tangle (microtubule)

alzeihmer’s disease - lack what neurotransmitter

ACh

alzheimer’s disease - diagnosis method

mini-mental status examination (MMSE)

MMSE - normal cognition range

24-30

MMSE - severe cognitive impairment range

≤ 9

rivastigmine - drug class

central cholinesterase inhibitor (ChEIs)

donepezil - drug class

central cholinesterase inhibitors (ChEIs)

galantamine - drug class

central cholinesterase inhibitors (ChEIs)

mild-to-moderate alzheimer’s disease - drug

rivastigmine

moderate-to-severe alzheimer’s disease - ChEIs

donepezil, galantamine

moderate-to-severe alzheimer’s disease - NMDA antagonist

memantine

moderate-to-severe alzheimer’s disease - general treatment

NMDA antagonist ± ChEI

parkinson’s disease - motor symptoms

TRAP (tremor at rest, rigidity, akinesia, postural & gait disturbance)

parkinson’s disease - pathological hallmarks

loss of nigrostriatal neurons (from substantia nigra), lewy bodies (α-synuclein)

parkinson’s disease - neurotransmitter levels

low dopamine, high ACh

enzymes that degrade dopamine

MAO-B, COMT

dopamine or ACh - which one stimulates cortex

dopamine

can dopamine cross BBB

no

precursor of dopamine that can cross BBB

L-dopa

first line treatment of parkinson’s disease

levadopa (L-dopa) + DDC inhibitors

dopa decarboxylase (DDC) inhibitor - examples

carbidopa, benserazide

dopa decarboxylase (DDC) inhibitor - mechanism

block peripheral conversion of L-dopa to DA

dopa decarboxylase (DDC) inhibitor - usage

in combination with L-dopa to prevent L-dopa degradation

D2 receptor agonist - mechanism

stim. D2 receptor → increase motor symptom

D2 receptor agonist - drug

bromocriptine

D2 receptor agonist - clinical use

mono & combination with L-dopa/carbidopa

dopa decarboxylase inhibitor - drug

carbidopa

MAO-B inhibitor - drugs

rasagiline, selegiline

COMT inhibitor - drugs

tolcapone, entacapone

dopa decarboxylase - function

convert L-dopa to dopamine

entacapone - mechanism

inhibit periphery L-dopa degradation (doesn’t cross BBB)

tolcapone - mechanism

inhibit central & peripheral L-dopa degradation (cross BBB)

tolcapone - ADRs

hepatotoxicity

COMT inhibitors - usage

in combination with L-dopa + DDC inhibitor

MAO-B inhibitors - usage

single drug or added to L-dopa + DDC inhibitor

selegiline - metabolized into

amphetamine

selegiline - ADRs

hypertensive crisis

central cholinergic antagonists - mechanism

block ACh receptor in neostriatum → decrease GABA → increase direct DA pathway

central cholinergic antagonist - clinical use instructions

add-on drugs in patients age < 60 yrs (avoid anti-cholinergic effects)