psych/neuro AD and PD

what are the main PD drugs?

(1) Levodopa therapy: carbidopa/levodopa

(2) DA agonists

(3) MAO-B Inhibitors

(4) NMDA-R antagonists: amantadine

(5) Anticholinergics

(6) COMT-Inhibitors

(7) Adenosine receptor antagonist (A2A)

what are the objective info for PD evaluation

neuro exam shows bradykinesia + tremor OR rigidity

what are the goals of PD treatment

reduce motor symptoms and reduce non-motor symptoms

what is the preferred dopaminergic therapy for PD

l-dopa

what class of PD drug is recommmended for pts <60 y/o

DA; they are at higher risk for dyskinesias

what class is used for mild motor symptoms in pts with early PD

MAO-B inhibitors

what are the different formulations for l-dopa

(1) IR - Sinemet

(2) ER - Rytary and Crexont

(3) enteral suspension - Duopa

(4) inhalation - Inbrija

what is the inital dose for Sinement

1/2-1 tab BID-TID over several weeks 10/100mg

wha tis the maintenance dose for Sinemet

find lowest dose based on clinical response, 300mg l-dopa total daily dose is usually an effective dose in the beginning

what is the max daily dose for l-dopa

2000mg daily

what are the adverse effects of l-dopa

(1) n/v

(2) GI upset

(3) orthostatic hypotension

(4) dyskinesias

t/f dyskinesias is avoidable in l-dopa treatment

false

what age group is l-dopa recommended for

>= 65 y/o

what should l-dopa be taken with

small meal (crackers), should avoid taking with high protein meal

how is l-dopa transported across membrane in gut

amino transporters

what is the 2nd most efficacious PD med

DA

what are examples of oral formulations of DA

(1) ropinirole

(2) pramipexole

what DA is a patch formulation

rotigotine

how is apomorphine administered

subQ or sublingual (only for emergencies)

what are the ADEs for DA

(1) nausea

(2) postural/orthostatic hypotension

(3) hallucinations

(4) sleep attacks

(5) ICD

are incidence rates of dyskinesias less in DA or l-dopa

DA

a pt should avoid DA if they have pre-existing:

ICD, sleep attacks, and cognitive disorders

what is QUIP-RS used to determine

ICD

when are MAO-B-I used

initial monotherapy or as adjunct with l-dopa

t/f MAO-B-I are modestly effective compared to DA and l-dopa

true

will initial treatment with MAO-B-I reduce risk of dyskinesias

yes

when should selegiline be taken

not in PM, amphetamine metabolite causes insomnia

what are the DDIs for MAO-B-I

opioids, SJW, dextromethorphan, triptans, tramadol, TCAs

what is serotonin syndrome

life-threatening condition who has excess 5-HT

what is the FDA warning for MAO-B-I + antidepressants

serotonin syndrome

how does MAO-B-I cause serotonin syndrome

MAO-B-I inhibit metabolism of 5-HT as well as DA, increasing risk of serotonin toxicity

what is the rationale for using anticholinergic agents for PD

DA and ACh usually in equilibrium in basal ganglia, but DA depletion causes imbalance

what is the indication for anticholinergic agents

<65 with mostly tremor

too many ADEs with age >=65 and not effective for other sx

what are the anticholinergic side effects

anti-SLUD

S - salivation - opposite is dry mouth

L - lacrimation - opposite is dry eyes

U - urination - opposite is urinary retention

D - defection -opposite is constipation

what is the DDI for amantidine

any DA blocking agents

ex: prochlorperazine (Compazine)

when does diagnosis of PD start

when approximately 70% of DA neurons are lost and motor symptoms start to appear

what is the wearing "off" phenomenon

med wears off, doesn't last, causing episodes of increased motor sx

what is the "on" phenomenon

at med peak, involuntary, abnormal excess movements occur called dyskinesias

when do you use l-dopa CR

@ PM to reduce middle of the night or early morning wearing off

when are COMT-I used

what are the main COMT-I used for PD?

what is the dosage of entacapone?

what is the BBW of tolcapone?

only used as adjunct to carb/l-dopa to extend half-life

(1) Entacapone

(2) Tolcapone

one tab (200mg) w/ each dose of cardiopda/levodopa

severe hepatotoxicity -- can be fatal

what is the indication of adenosine A2A receptor antagonist

adjunctive therapy for "off" periods

what are the DDIs of Adenosine receptor antagonist?

major = CYP3A4

what are the different ways you can manage off periods

⚫️extend l-dopa coverage by:

(1) increase l-dopa frequency

(2) add/switch to carb/l-dopa CR/ER

(3) add COMT-I

⚫️add another agent

(1) adenosine receptor antagonist

(2) MAO-I

(3) DA

(4) amantadine

what are the different ways you can manage on periods

(1) decrease l-dopa dose

(2) decrease l-dopa dose and add DA

(3) increase dosing interval of l-dopa

(4) try amantidine

PD ____ over decades with multiple _______ and _______ symptoms occuring as the disease _________

progresses; different; non-motor; worsens

what are the non-motor symptoms in PD

(1) urinary frequency

(2) constipation

(3) orthostatic hypotension

what are the non-motor psychiatric symptoms in PD

(1) sleep problems

(2) psychosis

(3) depression

(4) dementia (late stage)

what classes of drugs must be used with caution with MAO-B-I

SSRIs and TCAs

what is the gold standard for PD

carb/l-dopa, but complicated by development of motor fluctuations/dyskinesias

what are the inital treatments for PD

⚫️ any one these individually depending on age and symptoms

(1) MAO-B-I

(2) DA

(3) carb/l-dopa

a(4) nticholinergics/amantadine