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Anti Parkinson's Drugs
Anti Parkinson's Drugs
27
Medical
Post-Graduate
03/29/2010

Additional Medical Flashcards

 


 

Cards

Term
Parkinson's Disease
Definition
Neurodegenerative Disease due to decreased dopamine in the basal ganglia. causes impaired muscle movement
Term
Drug Induced Parkinsonism
Definition

neuroleptics -> haloperidol

metoclopramide -> DA Antagonist

Reserpine -> Depletes DA, NE

Carbamazepine -> Antiepileptic

MPTP -> neurotoxin, analog of meperidine

Term
FDOPA
Definition

High concentrations normally but low

concentrations in Parkinsons

Term
4 cardinal features
Definition

1. tremor

2. rigidity

3. bradykinesia / akinesia

4. disorders of gait and posture

Term

1. Tremor

 

2. Rigidity

 

3. bradykinesia/akinesia

 

4. disorders of gait and posture

Definition

1. first motor sign in 75% of patients pill rolling

 

2. increased resistance to passive movement. ratchety "cogwheel" motion.

 

3. slowness or absence of movement. drooling. masklike expressionless face w/ decreased blinking

 

4. festinating (catching up). freezing propulsion falling

Term
Surgical Therapies
Definition
Pallidotomy (remove globus pallidus) / Thalatomy (remove VL Thalamus)

Fetal Nigral Transplantation
Term
Pathophysiology
Definition

degeneration of Dopimanergic neurons in substantia nigra w/in basal ganglia leads to reduction of DA in the striatum.

 

The Nigrostriatal Pathway is part of the extrapyramidal system that regulates fine motor movement, muscle tone, and posture.

 

it modifies the output of descending motor pathway to turn gross uncoordinated movement into finely coordinated movements

Term
Levodopa
Definition

dopamine is polar and does not cross BBB, thus this drug is given.

 

rapidly absorbed from SI by active transport. Take on empty stomach. competes for active transport. 1st pass effect. thus only 1% enters CNS. give w/ carbidopa (an inhibitor of dopamine decarboxylase)

 

prodrug. interacts w/ D2.

 

 

 

Term
Levodopa
Definition

 

GI - NV and anorexia (give w/ carbidopa) CV - tachycardia, arrhythmias, postural hypotension


Abnormal involuntary movements: dyskinesias
- orofacial tics
-dose related (increased incidence w/ carbidopa)
-drug holiday not recommended

behavioral disturbances
- hallucinations, anxiety
- dose related (more common w/ carbidopa)


 

Term
Levodopa
Definition

"wearing off" or "end of dose" akinesia

-decrease w/ COMT inhibitors or Stalevo

 

"on off phenomenon" --> dyskinesia during on periods.

-decrease protein intake

-fluctuations may be lessened by taking smaller doses or prolonged release (Sinemet CR)

Term
Levodopa
Definition

Best results in first 3 to 4 years.

- after that refractoriness may develop or increased SE due to supersensitivity

- reserved for more advanced parkinsonism

- abrupt withdrawal causes severe akinesia

Term
Combination: carbidopa + levodopa(sinemet)
Definition

This drug is available alone or in fixed dose combos w/ levodopa.

 

sinemet - slower onset, longer duration.

 

sinemet cr -controlled release prep 

Term
Sinemet
Definition

carbidopa + levodopa allows you to 

- decrease levodopa dose by 75%

- NV less freq

- tachycardia less likely

-less fluctuation

- pyridoxine no longer antagonizes L-dopa

 

L-dopa alone - only 3% reaches CNS

L-dopa w/ carbidopa - 10% reaches CNS

Term
Sinemet
Definition

dyskinesias and psychiatric disturbances develop earlier and can be more severe

 

start low doses and increase gradually

 

caution: peptic ulcer, cardiac disease, open angle glaucoma (mydriasis)

 

contraindications: angle closure glaucoma, psychosis, malignant melanoma (L-dopa is a precursor to melanin)

Term
Sinemet
Definition

Drug interactions:

-pyridoxine

-MAO inhibitors (can cause hypertensive crisis)

 

Term
Bromocriptine
Definition

dopaminergic agonist

 

ergoline. used to treat hyperprolactinemia.

 

strong D2 agonist, weak D1 agonist

 

effects = Ldopa but weaker. works better when used w/ Ldopa.

Term
Bromocriptine
Definition

combined w/ Ldopa for "on off" phenom or "refractoriness"

 

alternative to Ldopa if contraindicated

 

SE

-CV - orthostatic hypotension

-dyskinesias - less than Ldopa

- more confusion

-erythromelalgia (red, tender lower extremities)

 

contraindications

-mental illness, CV disease, pregnancy

 

start low dose

Term

Pramipexole

Ropinirole

Rotigotine (transdermal patch)

Definition

Nonergot DA agonists

 

selective D2 agonist

 

Pram - excreted unchanged in urine

Rop - CYP1A2

Term

Pramipexole

Ropinirole

Rotigotine (transdermal patch)

 

Definition

alone for mild disease or in combo w/ Ldopa for advanced disease

 

to treat --> Restless Leg syndrome (more common in women)

 

SE --> sudden sleep attacks during daytime

Term
Selegiline
Definition

MAO-B inhibitor

 

lacks undesirable effects of non-selective MAO inhibitors

 

may have neuroprotective & anti-apoptotic effects

 

alone for early disease or adjunct w/ Ldopa for advanced disease. may decrease mild "on off" or "wearing off" phenom

Term
Selegiline
Definition

SE --> dyskinesias & mental disturbances

 

RxInteraction

-SSRI's - increase serotonin syndrome

-Meperidine - rigidity, agitation, delirium, tremens

Term

Tolcapone

 

(The Com Told Capone not to Drink Too Much or else his liver would fail)

Definition

COMT inhibitor

 

half life 2 hrs so given 4 to 6 times a day

 

adjunct to Ldopa

 

Adverse

- ND, hypotension

- Hepatotoxicity (Tolcaprone only)

Term
Amantadine
Definition

originally antiviral drug for Type A influenza

 

MOA

-increase DA release

-blocks DA reuptake

-blocks NMDA-Glutamate R

 

Adverse reactions

-CNS

-Livedo Reticularis - vasospastic disease (fishnet appearance)

Term

Trihexyphenidyl (prototype)

 

Benztropine mesylate

Definition

blocks central M-1 receptor

 

anticholinergic drug - decrease cholinergic activity from striatal neurons

 

Adverse reaction - confusion.

dry mouth, cycloplegia

 

Use - younger patients with mild early disease or drug induced parkinsonism

-adjunctive therapy w/ Ldopa

-Tremor and rigidity most improved but not bradykinesia

Term
Pathophysiology (Direct - to promote movement)
Definition

1. Cortex sends excitatory Glutaminergic NT to the Striatum

2. Striatum send Direct Inhibitory GABA to Globus Pallidus (GP) and Substantia Nigra pars reticulata (SNpr)

3. This causes GP & SNpr to stop inhibiting the Thalamus

4. Thalamus provides excitatory Glutamate to Cortex to promote movement

Term
Pathophysiology (Indirect - to inhibit movement)
Definition

1. Cortex excites Striatum w/ Glutamate

2. Striatum sends inhibitory GABA to GP

3. GP send GABA to subthalamic nucleus (STN) and disinhibits it

4. STN sends excitatory Glutamate to SNpr

5. SNpr sends GABA to Thalamus to inhibit movement

Term
Pathophysiology
Definition

1.  SNpc provides DA to striatum

 

2. DA excites the direct pathway via D1 and inhibits the indirect pathway via D2

 

3. In Parkinson's there is degeneration of DA neurons in SNpc thus depletion of DA

-This leads to overactivity of the indirect pathway 

-which increases the glutaminergic activity of the STN

- this leads to increased inhibition of thalamus and decreased excitatory input to motor cortex

-Thus HYPOKINESIA

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