Drugs-Dementia Flashcards
(52 cards)
An autosomal dominant genetic disorder in which mutations in the Huntingtin protein allow it to damage and progressively kill neurons in the brain; characterized by jerking or writhing movements (chorea), muscle problems, dystonia, etc.
Huntington Disease
The movement symptoms of HD is due to ____________ pathway that connects substantial nigra to the striatum.
nigrostriatal dopaminergic
Early-stage HD is characterized by an increased _______
dopamine
Examples of dopamine-depleting drugs
Tetrabenazine
Deutetrabenazine
drug that reduce the amount of dopamine that is released by nigrostriatal neurons by inhibiting the vesicular monoamine transporter (vMAT), which transports DA into presynaptic vesicles.
DA-depleting drugs (Tetrabenazine, Deutetrabenazine)
Examples of dopamine antagonists
Aripiprazole
Drug that directly compete with dopamine (DA) for binding to DA receptors on the post-synaptic cells
Dopamine antagonists (Aripiprazole)
Drugs that are also atypical 2nd generation anti-psychotics and may also treat agitation and psychosis associated with HD
Aripiprazole
Atypical 2nd generation anti-psychotics can antagonize several other, non-therapeutic receptors and can lead to other toxicities.
Antagonizing Ach receptors (M2/3) can cause
Constipation
Xerostomia
Urinary Retention
Blurred vision
Atypical 2nd generation anti-psychotics can antagonize several other, non-therapeutic receptors and can lead to other toxicities.
Antagonizing NE receptor (a1) can cause
Orthostatic hypotention
Atypical 2nd generation anti-psychotics can antagonize several other, non-therapeutic receptors and can lead to other toxicities.
Antagonizing histamine (H1) can cause
Sedation
Atypical 2nd generation anti-psychotics can antagonize several other, non-therapeutic receptors and can lead to other toxicities.
Antagonizing K+ channels can cause
P-QT sudden death
Atypical 2nd generation anti-psychotics can antagonize several other, non-therapeutic receptors and can lead to other toxicities.
Antagonizing Dopamine receptors (D2) beyond therapeutic effects can lead to toxic effects such as
EPS NMS Gynecomastia Amenorrhea Sexual Dys.
Atypical 2nd generation anti-psychotics can antagonize several other, non-therapeutic receptors and can lead to other toxicities.
Antagonizing serotonin receptors (5-HT) beyond therapeutic effects can lead to toxic effects such as
Metabolic syndromes (weight gain, hyperglycemia, hyperlipidemia, type 2 DM)
A dementia disorder caused by a progressive loss of dopaminergic neurons in the nigrostriatal pathway
Parkinsons’ Disease
Examples of DA precursor drug
Levodopa (L-DOPA)
Drug that is an intermediate in the biosynthesis of DA that can cross the BBB and enter remaining nigrostriatal neurons, where it gets converted into DA by DOPA decarboxylase (DDC)
Levodopa (L-DOPA)
What enzyme converts levodopa into dopamine in peripheral tissues?
DOPA decarboxylase (DDC)
An inhibitor of DDC; co-administered with levodopa to increase the amount of drug that reaches the brain for conversion into DA; itself doesn’t cross the BBB
Carbidopa
COMT inhibitors; typically added only after the therapeutic effects of levodopa + carbidopa begin to fluctuate or wear off following YEARS of use
Entacapone
Tolcapone
The phenomenon which results from the fact that there are fewer neurons available in later stages of the disease to convert levodopa to dopamine and store it as a neurotransmitter
“Wearing off” phenomenon of levodopa (+carbidopa)
Dyskinesia that follows hours of each dose of levodopa during the wearing off phase; it’s a toxicity from a long-term use of levodopa
levodopa-induced dyskinesia (LID)
Other toxicities of levodopa; can be exacerbated with the addition of COMT inhibitor
Nausea/vomiting
Orthostatic hypotension (at the beginning of therapy)
Psychosis
Toxicities caused by COMT inhibitors alone
Diarrhea
