Parkinsons Disease Drugs

Front 1

Is Alzheimers more common or PD more common?
At what age would a person get PD?

Back 1

Alzheimers
2. 40-70, after 70 you probs have something protective that will prevent you from getting it

Front 2

What is the primary physio disorder in PD? What happens to Ach?
What happens to fine motor control?

Back 2

1. Loss of dopaminergic neurons in substantia nigra.
2. Loss of balance and overactivity of Ach leading to abnormality in inhibitory output from basal ganglia
3. There is loss of inhibitory control by the basal ganglia on the reticular system leading to problems in controlling fine movement

Front 3

What are the 2 main methods of tx?

Back 3

- beef up the ramaining dopamine producing cells
- or weaken the Ach producing neurons

Front 4

What are the clinical sx of PD?

Back 4

Tremor- pill rolling, Ach overactivity
Rigidity- cogwheel
Akinesia/bradykinesia
Posture/gait abnormalities
- wll also see cog dysf, autonomic disturbances, micrographia, and masked facies

Front 5

What 4 classes of drugs are associated w/ drug induced PD?

Back 5

- dopamine antagonists
- neuroleptics-- like haloperidol
- phenothiazine antiemetic agents
- substituted benzamides-- pro motility agent metoclopramide

Front 6

How long after drug induced PD is dxed does it take to tx?

Back 6

Wks to monthes, but onset will be RAPID and will be bilateral

Front 7

Are PD meds for sx management or a cure? Can pts be taken off PD meds abruptly?

Back 7

Sx management

Front 8

Levodopa/Carbidopa- MOA

Back 8

- levodopa which is immediate precursor to dopamine will cross the BBB and carbidopa prevents peripheral conversion of levodopa to dopamine by inhibiting peripheral dopamine decarboxylase

Front 9

L/D- AE

Back 9

- for first 2-5 yrs of tx there is sustained response but as disease progresses the duration of benefit becomes shorter for each dose
- after 5-8 yrs pts have dose related complications-- sudden unpreditable fluctuations b/w mobility and immobility- "on-off" effect
- also can have dose related dyskinesias
- peripheral adverse effects- orth hypotension, anorexia
CNS SE- hallucinations-PARTICULARLY in pts that also have demetia

Front 10

Carbidopa- Use

Back 10

- inhibits peripheral dopamine conversion, w/o CD, LD would be converted to DA in periphery which would lead to N&V and orthostatic hypotension

Front 11

Levodopa- PK

Back 11

- 1/2 life 60-90 mins- some pts require 3-6 doses a day
- protein rich diet decreases absorption
- different formatulations include- controlled release CD/LD (should combo w/ immediate release as well), chewed or crushed tablets w/ carbonated beverage for rapid absorption in on off episodes

Front 12

CD/LD-Use

Back 12

- PD, is gold std but may accelerate neurodegeneration so is not the best med to give very young pt

Front 13

DA- MOA

Back 13

- stimulate dopamine receptors w/ dopamine agonists

Front 14

Ergot-derived DA- drug names and SE

Back 14

- pergolide, bromocriptine
- pukm and retroperitoneal fibrosis
- SE profile limits their use

Front 15

Non- ergot dopamine agonists (i.e. direct DA)- drug names

Back 15

- pramipexole, ropinirole
- rotigotine- transdermal formulation w/ once daily dosing

Front 16

DA- AE, names

Back 16

- names: parmipexote, ropinerole, rotigotine
- peripheral AE- nausea, lower extremity edema, and postural hypotension
- CNS side effects- can cause confusion and toxic psychosis particularily in elderly pts
- higher incidence of somnolence, edema, and hallucinatiosn than Levidopa
- should not be used in pts w/ dementia
- sudden sleep attacks- preceded by prodrome phase
- impulse control disorders

Front 17

DA-Use, names

Back 17

- less likely to produce dyskenisias down the road
- less N&V and orthostatic hypotension than CD/LD
- less effective than CD/LD
- more CNS SE
- good for EARLY mild disease, can be added to levodopa in late disease to reduce off time
Names- parimipexote, ropinirole, rotigotine

Front 18

Apomorphine- Class, Use, SE

Back 18

- Class- injectable DA
- Use: for acute intermittent tx of episodes of immobility in pts w/ advanced PD
- SE- use limited by severe nausea, ortho hypotension, hypersexuality, dyskenisias, hallucinations

Front 19

Apomorphine should be given w/ what meds prophylactically?
Which drugs should not be given w/ apomorphine?

Back 19

- oral domperidone to block emesis
- serotnin receptor antagonist- class of anti emetics which are contraindicated b/c cause severe hypotension and loss of consciousness

Front 20

COMT Inhibtors- MOA, USE

Back 20

- Use- in combo w/ levodopa to inhibit peripheral activity of COMT (which converts levodopa to dopamine)- thus will increase amt of levodopa that can cross BBB
- MOA- levodopa is metab in periphery by dopa decarb and by COMT
-

Front 21

ENtacapone- Class, PK, Use

Back 21

COMT Inhibitor
PK: short half life and must be taken w/ each dose of levodopa
Use: useful w/ wearing off phenomenon of levodopa and will provide longer duration of action later in disease

Front 22

Entacapone- Class, AE

Back 22

COMT inhibtor
- dyskiniseas, diarrhea, and urine discoloration
- SERIOUS hepatotoxicity- hepatic monitoring imp

Front 23

MAO Inhibitors- MOA, Names

Back 23

Binds to and inhibit MAOB, preventing dopamine degradation. This results in greater stores of dopamine available for release
- saligiline, rasagiline

Front 24

MAO-B Inhibitors:
Selegiline: Use
Rasagiline:Use

Back 24

Selegiline- irreversible inhibitor of MAOB, modest effect on disease, used as MONOTHERAPY early in disease and delays initiation of levodopa tx. In advanced disease used IN ADDITION to levodopa to lower levodopa dose.
Rasagaline: monotherapy early in disease or in addition in late disease, improvement in OFF TIME in late disease

Front 25

Selegiline- Class, AE, Contraindications

Back 25

Class: MAO B Inhibitor
AE: looses MAO B selectivity at doses greater than 10 mg/day, nause, hallucinations, and orthostatic hypotension
CI: meperidine, can also increase levodopa SE, particularly dyskinesias and psychosis in elderly pts

Front 26

Rasagiline- Class, AE, CI

Back 26

Class; MAOB inhibitor
AE: selectivity for MAO B not definitively established. Also causes nausea, hallucinations, and orthostatic hypotension. Can also increase AE of levodopa, particularly dyskinesias and psychosis in elderly pts
CI: B/c selectivity not well established, do NOT administer w/ propoxyphene, tramadol, methadone, dextromethorphan, sympathomimetics, SSRIs.
Do NOT administer w/ meperidine. Avoid tyramine rich foods such as wine and cheese

Front 27

Anticholinergics- MOA, Use

Back 27

MOA- blocks Ach receptors which will help to correct the dopamine- Ach imbalance.
Use: helps w/ management of parkinsonian tremor and is effective for drooling

Front 28

Anticholinergics- AE, CI

Back 28

Peripheral AE- dry mouth, constipation, urinary retention, and aggravation of glaucoma
CNS AE: impaired memory, confusion, hallucinations
- anticholinergic agents are not commonly used to tx PD due to AE and inability to improve dyskinesias
- all AE particularly severe in elderly pts and are CONTRAINDICATED at this age group

Front 29

Amantadine-Use, MOA

Back 29

Use; antiviral w/ antiparkinsonian properties, used alone to ts EARLY MILD sx of PD< much less effective than Levodopa, only 3-6 mos, used as adjunct later and reduces dyskinesias at this stage
MOA: antagonist at glutamate receptors, which may decrease xs neurotransmission by glutamate and possibly enhance dopamine release and inhibit its reuptake

Front 30

Amantadine- AE

Back 30

-nausea, dizziness, insomnia, confusion, hallucinations, and livedo reticularis
- severe psychosis in elderly at high doses

Front 31

Dyskinesias are ____ movements, dystonia and chorea are the most common and worsen over time. These sx often occur when sx of PD are under ____ control w/ ____, likely due to ____ receptor ____, which changes NT signalling in basal ganglia.
How to prevent?
Tx strategy?

Back 31

1. involuntary
2. good control
3. LD/Carpidopa
4. dopamine receptor
5. overstimulation
6. delay initiation of LD/CD
7. smaller more freq doses of LD/CD, reduce LD and increase dose of dopamine agonist, and also initiating amantadine-- has some dyskinetic effect in some pts

Front 32

Over time neurons lose ability to store dopamine, once stored dopamine is depleted sx will return. Strategies to offset wearing off: 1. , 2., 3.

Back 32

1. increasing dose of LD/CD or shortening interval b/w doses
2. use of controlled release LD/CD
3. concomitant use of LD sparing meds-- COMT inhibitor which slow breakdown of LD, addition of DA, and/or MAO B inhibitor

Front 33

What is the difference b/w the on/off phenomenon and wearing off?

Back 33

On/off phenonmenon is unpredictable. On/off is charachterized by sudden worsening of sx that resolves spontaneously

Front 34

Causes of psychosis in PD pts?
Type of hallucinations?
Tx necessity?

Back 34

1. can be due to PD or tx w/ dopaminergic agents
2. tend to occur w/ intact sight, very vivid but early on are not frightening may become more distressful as time progresses, no need to tx if caretaker and pt are not bothered
- taper off offending agent, if tapering results in increase of PD sx add antipsychotic agent instead (but not D2 receptor antagonists)

Front 35

Drugs used to tx psychosis in PD?

Back 35

D2 receptor antagonists should be AVOIDED. Clozapine preserves motor fx but causes sz, myocarditis, and ortho hypotension
- quetiapine- FIRST CHOICE

Front 36

What is rescue drug in pts w/ severe on-off episodes?

Back 36

- subQ apomorphine- injectable DA