Pharm Pino: Parkinson's and Alzheimers

metabolized by dopa carboxylase to dopamine

will cross the BBB (unlike dopamine) in the brain and replaces the missing dopamine

treats Parkinson’s disease

levodopa (l-dopa)

drug interactions:

high protein foods decrease its absorption

vitamin B6 increases its decarboxylation

levodopa (l-dopa)

adverse effects: n/v (DA increased in the chemotrigger zone)

orthostatic hypotension

cardiac arrhythmia

hallucinations and delusions

“on-off” phenomena

levodopa (l-dopa)

does not cross the BBB

blocks dopa decarboxylase in the periphery (prevents drug breakdown in periphery)

used as an adjunct to treat Parkinson’s (doesn’t actually treat it itself)

carbidopa

What is a positive effect of carbidopa?

it lowers the amount of levodopa needed, so it in turn lowers the toxicities and adverse effects of levodopa (l-dopa)

D3 receptor agonist (associated with compulsive behavior and impulse control effects)

helps make consistent dopamine resopnse

can be used alone or with l-dopa to reduce the on-off phenomena

pramipexole

D2 and D3 receptor agonist. Decrease free radicals

ropinirole

bromocriptine

rotigotine

What drugs can also be used to treat restless leg syndrome?

pramipexole and ropinirole

_____ treats elevated prolactin levels as well as Parkinsons

bromocriptine

Dopamine receptor agonist in the caudate nucleus and putamen

“emetic”

Used sc, sl or IV to “rescue” patient when L-Dopa is in severe off phenomena and dyskinesia

apomorphine

adverse effects:

nausea and vomiting that can be managed by trimethobenzamide

increased QT interval

apomorphine

MAO-B inhibitors

Block metabolism of dopamine, improve action of levodopa and therapy of Parkinson’s

helps with “off” episodes

Selegiline (irreversible)
Rasagiline (irreversible)
Safinamide (reversible

Which MAO-B inhibitor also decreases glutamate release

Safinamide

_____ drugs do not have interaction with tyramine foods unlike ____ which do

MAO-B do not but MAO-A do

____ is the MAO-B inhibitor that makes metabolites that are amphetamine-like and can cause serotonin syndrome

Selegiline

______ is an MAO-B inhibitor that is not indicated in hepatic impairment

Safinamide

What are the COMT inhibitors?

tolcapone, entacapone, opicapone

explain the differences between tolcapone and entacapone

tolcapone crosses both BBB and periphery (good except an adverse effect is possible hepatitis)

entacapone is peripheral only (doesn’t cause hepatitis but also doesn’t cross BBB)

Muscarinic block in basal ganglia

Reduces tremor and rigidity. Balance hypothesis (Dopamine vs Ach)

Benztropine and Trihexyphenidyl

adverse effects: antimuscarinic (aka sympathetic)

sedation, mydriasis, cycloplegia, dry mouth and skin, tachycardia, constipation, and
delirium

Benztropine and Trihexyphenidyl

NMDA receptor antagonist
Muscarinic blocker
Releases DA (antiviral treats influenza A, blocks uncoating of M2 channel)

Amantadine

adverse effects:

Psychosis
Skin changes (livedo reticularis)
Muscarinic blockade adverse effects

Amantadine

blocks adenosine

Selective adenosine A2A receptor antagonist

Regulates GABAergic neurotransmission in the basal ganglia

Helps “off phenomena”

adverse effects: Insomnia and Loss of appetite

Istradefylline

What do we use to treat Huntington’s chorea?

Tetrabenazine

inhibits VMAT-2 resulting in decreased uptake of monoamines

Tetrabenazine (treats huntington’s chorea)

What drugs are antipsychotics that are known to cause parkinsonism, tarditive dyskinesia, and elevated prolactin?

D2 receptors ANTAGONISTS

Haloperidol
Fluphenzine
Chlorpromazine

What drugs are antiemetics that are known to cause parkinsonism?

D2 receptors ANTAGONISTS

Metoclopramide and Prochlorperazine

What drugs are the cholinesterase inhibitors that are used to treat alzheimer’s

Donepezil
Rivastigmine
Galantamine
Tacrine

adverse effects:

Muscarinic agonist actions (Parasympathetic)
Increased toxicity with CYP P450 inhibitors

Donepezil
Rivastigmine
Galantamine
Tacrine

NMDA Receptor Antagonist
Uncompetitive (glutamate)

blocks pathological glutamate but not physiological

Memantine

Monoclonal antibody that targets amyloid beta

Aducanumab Donanemab Lecanemab

Which one is monthly administration?

Aducanumab and Donanemab and Lecanemab

Donanemab

Specific for toxic protofils. Administration every 2 weeks

Lecanemab

adverse effects: ARIA and ARA

MRI to be performed at specific intervals to infusions

Aducanumab
Donanemab
Lecanemab

What are the drugs whose adverse effects include parkinsonism

chlorpromazine, fluphenzine, haloperidol, tetrabenazine, metoclopramide, and prochlorperazine

(crazy folks here), tetra, (me puke)

which cholinesterase inhibitor also inhibits butyrylcholinesterase?

rivastigmine

D2/D3 receptor agonists vs D2 antagonists

agonist: ropinorole, bromocriptine, and rotigotine

antagonist: (crazy folks here) chlorpromazine, fluphenzine, haloperidol, metoclopramide, and prochlorperazine