Medications for neurodegenerative diseases Flashcards
What is the genetics of HD ?
10 to 35 times of CAG repeat that gives raise to Huntington gene on chromosome 4.
CAG codes for aminoacid____________.
Glutamine
Why is HD a polyglutamine disease ?
It is a triple repeat disorder in which there is excessive glutamate due to the presence of >36 glutamate in each CAG repeat.
What is the microscopic pathology of HD ?
exitotoxic neuronal cell death in caudate and putamen.
What is the neurotransmitter derangement seen in HD ?
decrease in inhibitory neurotransmitor like GABA and increase in excitatory neurotransmitters such as dopamine. In addition acetylecholine released by the inter-neurones and involved in neuronal communication are also decreased in HD.
What are the dopamine antagonists used in HD ?
Tetrabenazine, Dutetetrabenazine and antipsychotics.
How does Tetrabenazine, Dutetetrabenazine work (MOA)?
They work on both pre and post synaptic neurones. In the pre-synaptic neurones they block vesicular monoamine transporters (VMAT) leading to impaired dopamine storage into the synaptic vesicles. On the post synaptic neurones these medications act as a partial dopamine antagonists. These action in effect reduce chorea.
What other condition is treated with Tetrabenazine, Dutetetrabenazine?
The tics of Tourret syndrome.
What are the side effects of Tetrabenazine, Dutetetrabenazine?
Worsening of depressive symptoms, increase the risk of suicide, psuedoparkinsonism and sedation.
What are the preferred agents to HD if chorea along with psychosis and agitation are present ?
2nd gen. Antipsychotics such as Olanzapine and resperidone are preferred. However, more potent first gen. antipsychotics such as haloperidole are also used.
Osmosis link to Medications for neurodegenerative diseases
https://www.osmosis.org/learn/Medications_for_neurodegenerative_diseases?from=/pa/foundational-sciences/pharmacology-and-pharmacotherapeutics/neurologic-system/neurodegenerative-disease-medications/other-neurodegenerative-diseases
