Alzheimers Med Chem Flashcards
Alzheimers is a neurodegenerative disorder that can be a result of a neurochemical deficiency in ___.
A. GABA
B. ACh
C. AChE
D. BuChE
B. ACh
In order to produce Acetylcholine (ACh) you need ___ and ___
A. CoA, Choline
B. Acetyl-CoA, Dopamine
C. Acetyl-CoA, Choline
D. Dopamine, Choline
C. Acetyl-CoA, Choline
What enzyme is required in the biosynthesis of Acetylcholine (ACh)?
A. ChAT
B. AChE
C. BuChE
D. COMT
A. ChAT
Acetylcholinesterase (AChE) will work on carbon side chains up to __ carbons in length.
A. 1
B. 2
C. 3
D. 4
C. 3
AChE will primarily metabolize groups that are 3 carbons or less
Look at slide 7 for deactivation with BuChE
Tacrine HCl (Cognex) contains a functional group known as ___.
A. Cycloamine
B. Aminoacridine
C. Trietylamine
D. Imide
B. Aminoacridine
When looking at the metabolism of Tacrine, The Reactive Quinone Methide metabolite can possibly cause ___.
A. Neurotoxicity
B. Hepatotoxicity
C. Nephrotoxicity
D. Cardiotoxicity
B. Hepatotoxicity
Also note that the 1-OH Tacrine metabolite on the right-side is an active metabolite.
What enzyme metabolizes Tacrine?
A. CYP3A4
B. CYP2D6
C. CYP1A2
D. CYP2E1
C. CYP1A2
(Short Answer) Rivastigmine is known as a Psudo-Irreversible cholinesterase inhibitor (ChEI). Why is this?
Rivastigmine is known as pseudo-irreversible because unlike other cholinesterase inhibitors it takes longer for the bond between the drug and the cholinesterase enzyme to be hydrolyzed. The carbamate group in red wil form a bond with the Serine OH group on the cholinesterases (AChE, BuChE) and the hydroxylation to break them apart is much slower. When the carbamate group and the cholinesterase are bound to gether it is known as a Carbamylated AChE.
Donepezil (Aricept) has a higher affinity for ___ in the ___.
A. AChE, CNS
B. BuChE, CNS
C. AChE, Periphery
D. BuChE, Periphery
A. AChE, CNS
What is the name of the functional group circled in Donepezil (Aricept)?
A. Pyrazine
B. Pyridine
C. Piperazine
D. Piperidine
D. Piperidine
Zine= 2 nitrogens
Dine= 1 nitrogen
Piper= No double bonds
Pyra= Double bonds
PiperaDine= No double bonds with 1 nitrogens
Donepezil (Aricept) is a __ and reversible AChE inhibitor.
A. Competitive
B. Non-Competitive
B. Non-Competitive
In other words it does not compete with anything at the binding site for AChE. It binds elsewhere on the AChE.
Note: He could say that Donepezil is known as a piperidine non-competitive and reversible inhibitor of AChE.
What type of metabolism is occuring in Donepezil (Aricept) in reaction D?
A. Hydroxylation
B. N-Demethylation
C. O-Demethylation
D. Reduction
C. O-Demethylation
What type of metabolism is occuring in Donepezil (Aricept) in reaction C?
A. Hydroxylation
B. N-Dealkylation
C. N-Demethylation
D. N-Depropylation
B. N-Dealkylation
What type of metabolism is occuring in Donepezil (Aricept) in reaction B?
A. N-hydroxylation
B. N-Methylation
C. N-Oxidation
D. N-Carbamation
C. N-Oxidation
What type of metabolism is occuring in Donepezil (Aricept) in reaction A?
A. Hydroxylation
B. Reduction
C. Methylation
D. Carbamation
A. Hydroxylation
When looking at the metabolite in position D, which of the following statements is true regarding the 6-O-Desmethyl metabolite?
A. The 6-O-Desmethyl metabolite is an inactive toxic metabolite of donepezil
B. The 6-O-Desmethyl metabolite is an equi-active metabolite of donepezil
C. The 6-O-Desmethyl metabolite of Donepezil displays more potency than the parent drug molecule.
D. The 6-O Desmethyl metabolite of Donepezil is known to cause extreme cases of neurotoxicity
B. The 6-O-Desmethyl metabolite is an equi-active metabolite of donepezil
Galantamine (Razadyne) has dual cholinergic activity. Which of the following mecahnisms represents the dual activity of this drug? (Select All)
A. AChE inhibition
B. BuChE Inhibition
C. Negative allosteric modulation of nACh receptors
D. Positive allosteric modulation of nACh receptors
A. AChE inhibition
D. Positive allosteric modulation of nACh receptors
positive allosteric modulation of nAChRs means that it increases the succeptiblity of the receptor to ACh.
The following picture shows the metabolism of Galantamine using CYP3A4. What type of metabolite is displayed here?
A. O-Desmethyl
B. Normethyl
C. N-methylation
D. O-Desmethylnormethyl
B. Normethyl
The following picture shows the metabolism of Galantamine (Razadyne) using CYP2D6. What type of metabolite is formed in this reaction?
A. Normethyl
B. N-Methylation
C. O-Desmethyl
D. O-Desmethylnormethyl
C. O-Desmethyl
The following picture shows the metabolism of Galantamine (Razadyne) by CYP2D6. What type of metabolite is produced here?
A. O-Desmethylnormethyl
B. O-Desmethyl
C. N-Desmethyl
D. N-methylation
A. O-Desmethylnormethyl
Memantine (Namenda) is known as a(n) ___ derivative. This is due to blue cage-like structure circled in the picture.
A. Cyclopental
B. Cyclooctal
C. Dibunatane
D. Adamantane
D. Adamantane
