Huntington's Disease Pathophysiology and Drugs

Define chorea

Irregular, unpredictable, involuntary muscle jerks in various body parts

Describe the inheritance pattern of Huntington's disease

Autosomal dominant

Describe the progression of Huntington's disease

Progressive chorea and dementia

Cognitive decline and uncontrollable gait and limb motions

What is Huntington's disease related to?

An imbalance of DA, ACh and GABA

Chorea is a function of EXCESSIVE DA

What is the MOA of reserpine?

Impairs DA transmission

Depletes central catecholamines

What is the MOA of phenothiazines?

Blocks DA-R

What drugs are VMAT2 inhibitors?

Tetrabenazine

Deutetrabenazine

Valbenazine

Tetrabenazine

Xenazine

What is the MOA of tetrabenazine?

Anti-choreic drug depleting monoamines in nerve terminals

Describe the metabolism of tetrabenazine

CYP2D6 and CYP1A2 metabolism

What is the half-life of tetrabenazine?

6 hours

What are AEs of tetrabenazine?

Somnolence and insomnia, depression, anxiety, irritability, obsessive tendencies, akathisia, PD-like symptoms, dizziness, unsteady gait, nausea and vomiting

Deutetrabenazine

Austedo

How does deutetrabenazine compare to tetrabenazine?

Isotopic isomer of tetrabenazine

What is the MOA of deutetrabenazine?

Depletes monoamines in nerve terminals

Describe the metabolism of deutetrabenazine

CYP2D6, CYP1A2, and CYP3A4 metabolism

What is the half-life of deutetrabenazine?

9-10 hours

What are AEs of deutetrabenazine?

Somnolence > insomnia, diarrhea, UTI, anxiety, constipation, and confusion

Valbenazine

Ingrezza

What is the MOA of valbenazine?

Decreases vesicular concentration of monoamines

Describe the metabolism of valbenazine

CYP3A4 metabolism

What is the half-life of valbenazine?

15-22 hours

What are AEs of valbenazine?

Somnolence, akathisia, balance disorders, increases blood glucose and weight, anxiety, hyperprolactinemia