Treatment of Alzheimers/ Dementia

Question 1

Donepezil:

Answer 1

Reversible ACh-E Inhibitor
T1/2= 70 hours
-100% bioavailability & easily crosses the BBB
-Mild-Moderate treatment of AD/ Dementia
-40% plasma protein binding

Question 2

Galantamine:

Answer 2

-Reversible ACh-E Inhibitor
-T1/2= 7 hours
-Treats mild- moderate AD/ Dementia
80-100% bioavailability & crosses the BBB easily
-18% plasma protein binding
–SLEEPING AID

Question 3

Rivastigmine:

Answer 3

-Butyrlcholinesterase/ ACh-E Inhibitor
-Treats mild- moderate AD/ Dementia
T1/2= 1.5 hours
40% bioavailability & easily crosses the BBB
-40% plasma protein binding
–>Bipasses P450 CYP enzymes

Question 4

Memantine:

Answer 4

Non competitive, low affinity NMDA receptor antagonist

• Creates a partial block @ therapeutic doses
• -Sensitive to Na+, K+ and Ca2+ with a Mg2+ block
• Blocks n-ACh receptors
• Treats moderate- severe AD/ dementia & works for people intolerant with ACh-E inhibitors

Question 5

Nitromemantine:

Answer 5

• NTG + Memantine to enhance targeting & binding to extra synaptic NMDA receptors
• Nitrosylates NMDA receptors causing desensitization

Question 6

Valproic Acid (VPA):

Answer 6

• Shown to reduce/ prevent formation of beta- amyloid deposits in transgenic mice
• ->Eventually want to test in humans

Question 7

Pioglitazone:

Answer 7

Stimulates beta- amyloid clearance & the reversal of cognitive deficits in mice

Question 8

Gingko Biloba & Vitamin E:

Answer 8

Possible anti-oxidant therapies to block neurotoxicity of beta- amyloid
-In too high doses, anti-oxidants can be harmful