Module 1 MSN 672 Questions With Complete Solutions
D2 receptors in the indirect motor pathways learn to have TD
when what occurs?
when D2 blockage has become chronic
What is the mechanism that causes the indirect pathway to flip
from too much stop to too much go?
abnormal neuronal plasticity causing the proliferation of too
many and too sensitive D2 receptors in the indirect pathway
The emergence of involuntary movements in TD should be
monitored using what?
a neurologic examination and a rating scale such as the AIMS
(abnormal involuntary movement scale)
Are patients with mood disorder at greater risk for TD?
They are at greater risk
Most patients experience an immediate worsening of their
movements when D2 blockade is eliminated due to what?
The completely unblocked actions of dopamine in the absence
of any D2 antagonist therapy at all often make drug
discontinuation not an option in the treatment of TD
Recent developments show that TD can now be treated by what?
inhibiting the vesicular monoamine transporter type 2 (VMAT2)
Presynaptic transporters are localized where?
,on the presynaptic axon terminal and are well known as reuptake
pumps targeted by many drugs for depression
Transporters for neurotransmitters inside of the neurons are
located where?
on the synaptic vesicles and called vesicular transporters
The specific transporter known as VMAT2 is located on
synaptic vesicles inside of what neurotransmitters?
Dopamine, norepinephrine, serotonin, and histamine neurons
VMAT2 acts to store intraneuronal neurotransmitters until
when?
they are needed for release during neurotransmission
VMAT2 can also transport certain drugs as what?
false substrates such as amphetamines and Ecstasy, and these
false substrates compete with true neurotransmitter and block it
from being transported
There are two known types of VMAT inhibitors what are they?
reserpine which irreversibly inhibits both VMAT1 and VMAT2,
and tetrabenazine-related drugs which reversibly inhibit only
VMAT2
That is why reserpine and not tetrabenazine-related drugs are
often associated with what?
frequent peripheral side effects such as orthostatic hypotension
Tetrabenazine preferentially affects what at clinical doses?
dopamine transport
, When Tetrabenazine-related drugs block the transport of
dopamine into presynaptic vesicles what happens?
dopamine is rapidly degraded by monoamine oxidase (MAO)
within the presynaptic neuron leading to depletion of
presynaptic dopamine proportional to the degree if VMAT2
inhibition
Tetrabenazine itself is actually an inactive3 prodrug converted
into four active dihydro metabolites by the enzyme carbonyl
reductase and all four are inactivated by what?
CYP450 2D6
Tetrabenazine is not approved for the treatment of TD but it is
approved for what?
the chorea of Huntington's disease
Valbenazine is approved for treatment in TD and does not
require what?
no need for genetic testing, for dosing with food, once daily
dosing, and no suicide warning
VMAT2 inhibition is a mechanism that reduces dopamine
without doing what?
blocking D2 receptors
VMAT2 inhibition would be expected to do what in the direct
pathway?
lower the go signals
D2 receptors in the indirect motor pathways learn to have TD
when what occurs?
when D2 blockage has become chronic
What is the mechanism that causes the indirect pathway to flip
from too much stop to too much go?
abnormal neuronal plasticity causing the proliferation of too
many and too sensitive D2 receptors in the indirect pathway
The emergence of involuntary movements in TD should be
monitored using what?
a neurologic examination and a rating scale such as the AIMS
(abnormal involuntary movement scale)
Are patients with mood disorder at greater risk for TD?
They are at greater risk
Most patients experience an immediate worsening of their
movements when D2 blockade is eliminated due to what?
The completely unblocked actions of dopamine in the absence
of any D2 antagonist therapy at all often make drug
discontinuation not an option in the treatment of TD
Recent developments show that TD can now be treated by what?
inhibiting the vesicular monoamine transporter type 2 (VMAT2)
Presynaptic transporters are localized where?
,on the presynaptic axon terminal and are well known as reuptake
pumps targeted by many drugs for depression
Transporters for neurotransmitters inside of the neurons are
located where?
on the synaptic vesicles and called vesicular transporters
The specific transporter known as VMAT2 is located on
synaptic vesicles inside of what neurotransmitters?
Dopamine, norepinephrine, serotonin, and histamine neurons
VMAT2 acts to store intraneuronal neurotransmitters until
when?
they are needed for release during neurotransmission
VMAT2 can also transport certain drugs as what?
false substrates such as amphetamines and Ecstasy, and these
false substrates compete with true neurotransmitter and block it
from being transported
There are two known types of VMAT inhibitors what are they?
reserpine which irreversibly inhibits both VMAT1 and VMAT2,
and tetrabenazine-related drugs which reversibly inhibit only
VMAT2
That is why reserpine and not tetrabenazine-related drugs are
often associated with what?
frequent peripheral side effects such as orthostatic hypotension
Tetrabenazine preferentially affects what at clinical doses?
dopamine transport
, When Tetrabenazine-related drugs block the transport of
dopamine into presynaptic vesicles what happens?
dopamine is rapidly degraded by monoamine oxidase (MAO)
within the presynaptic neuron leading to depletion of
presynaptic dopamine proportional to the degree if VMAT2
inhibition
Tetrabenazine itself is actually an inactive3 prodrug converted
into four active dihydro metabolites by the enzyme carbonyl
reductase and all four are inactivated by what?
CYP450 2D6
Tetrabenazine is not approved for the treatment of TD but it is
approved for what?
the chorea of Huntington's disease
Valbenazine is approved for treatment in TD and does not
require what?
no need for genetic testing, for dosing with food, once daily
dosing, and no suicide warning
VMAT2 inhibition is a mechanism that reduces dopamine
without doing what?
blocking D2 receptors
VMAT2 inhibition would be expected to do what in the direct
pathway?
lower the go signals
