Schriefer: Antiparkinson Agents

Front 1

a prevalent neurologic disorder characterized by progressive motor dysfunction due to tremor, rigidity, bradykinesia and disturbance of posture

Back 1

Parkinson’s disease (PD)

Front 2

The signs and symptoms of PD are due to the progressive degeneration of the inhibitory ___________pathway projecting from the substantia nigra to the caudate nucleus. Thus, individuals with PD have a deficiency of ____________..

Back 2

Dopaminergic


Dopamine

Front 3

In PD, there is a deficiency of dopamine, allowing ________________dominance.

Back 3

Cholinergic

(Neurochemical Defect)

Front 4

What is the MoA of Levodopa?

Back 4

Increase function of nigrostriatal dopaminergic pathway. activity is due to conversion to dopamine in CNS, thus increasing dopamine in the basal ganglia.

Front 5

What effect does L-dopa have on bradykinesia, rigidiy, and tremors?

Back 5

Bradykinesia and rigidity are reversed quickly; reversal of tremor requires CONTINUED therapy.

Front 6

Effect of Levodopa on mood and dementia?

Back 6

Changes in mood associated with PD are REVERSED; patients more alert and interested in environment. Dementia may NOT reverse.

Front 7

Effect of Levodopa on cardiovascular system?

Back 7

Dopamine stimulates both alpha and beta receptors. This resultsn asymptomatic orthostatic HYPOTENSION and cardiac stimulation.

Front 8

What effect will levadopa have on prolactin?

Back 8

Increased dopamin = increased INHIBITION of prolactin. Little change in GH secretion.

Front 9

Levadopa is acid labile. What can alter its absorption?

Back 9

1. Dec rate of gastric emptying
2. low pH
3. Degradation of enzymes
4. Competes with dietary protein (big mac).

Front 10

What must you be considered about when Levadopa is in the peripheral circulation?

Back 10

95% of L-dopa is metabolized in the periphery to dopamine; metabolism may be INCREASED with prolonged therapy.

Front 11

What is Parcopa?

Back 11

Orally dissolving, immediate release dopa + carbidopa mixture now available. Decreases peripheral metabolism of dopamine.

Front 12

What are the early side effects of Levadopa on 1. GI and 2. Cardiovascular system?

Back 12

1. NV
2. Orthostatic hypotension and cardiac arrhythmias.

Front 13

Psychiatric/behavioral disturbances, DYSKINESIA, and "On-Off Syndrome" are short term or long term adverse effects of Levadopa?

Back 13

Long Term

Front 14

Oscillations in performance involving rapid changes from akinesia to dyskinesia (different from “end of dose”).

Back 14

"On Off" syndrome from long term use of Levadopa.

Front 15

What is the effect of Pyridoxine (Vit B6) on Levadopa?

Back 15

Pyridoxine (vitamin B6) increases peripheral conversion of dopa to dopamine. Less dopamine into CNS!

Front 16

Why should you give an ATYPICAL anti-psychotic to a pt on Levadopa?

Back 16

Typical antipsychotic drugs are dopaminergic antagonists and thus counteract the effects of dopa.

Front 17

Why should Phenelzine or Tranylcypromine (MAOI's) not be given with Levadopa?

Back 17

MAO inhibitors increase the effects of dopa, may lead to hypertensive crises.

Front 18

What effect do anti-cholingeric drugs have on Levadopa's absorption?

Back 18

anticholinergic drugs may slow gastric emptying time and DECREASE absorption of 1 dopa.

Front 19

What effect will tricyclic antidepressents have on a pt taking Levadopa?

Back 19

Tricyclic antidepressants may aggravate hypotensive symptoms.

Front 20

What is the enzyme responsible for peripheral conversion of dopa to domapine?

Back 20

L-aromatic amino acid decarboxylase is responsible for the conversion of dopa to dopamine. Its activity causes 95% of a dose of dopa to be converted to dopamine before entering the CNS.

Front 21

What drug inhibits peripheral decarboxylase and allows greater amounts of dopa to enter the CNS?

Back 21

Carbidoipa

Front 22

What drug allows reduciton of dopa dose, decreases NV, decreases cardiac AR's, and pyriodoxine antagonism is gone compared to Levadopa?

Back 22

Carbidopa

Front 23

What drug may increase central side effects of dopa like Dyskinesia?

Back 23

Carbidopa

Front 24

What drugs inhibit COMT, thereby increasing the duration of action of l-dopa and dopamine (COMT inactivates l-dopa and dopamine).

Back 24

Tolcapone & Entacapone.
Capone was a chicago organized mob.

Front 25

What drugs AR is diarrhea, bright yellow discoloration of urine, increased l-dopa side effects?

Back 25

Entacapone

Front 26

Why is Entacapone more widely used than Tolcapone?

Back 26

Even though Tolcapone is more lipid soluble and reaches CNS, there hepatoxicity invovled.

Front 27

What drug is an adjunct to l-dopa in patients with stable PD and in patients with end of dose (“wearing off”) problems with l-dopa/carbidopa therapy?

Back 27

Entacapone

Front 28

What drug is a combination of carbidopa + 1-dopa + entacapone?

Back 28

Stalevo

Front 29

This drug is a D2 agnoist that causes cause direct stimulation of DA receptors rather than relying on DA neurons to convert l-dopa to DA.

Back 29

Ropinirole

Front 30

This drug is a D3 agnoist that causes direct stimulation of DA receptors rather than relying on DA neurons to convert l-dopa to DA.

Back 30

Pramipexole

Front 31

What two drugs may Produce less dyskinesia and lower incidence of response fluctuation. They may also have a neuroprotective effect so that progression of disease is slowed?

Back 31

ropinirole and pramipexole

Front 32

What drugs may cause nausea, dizziness, somnolence, headache, hallucinations, impulse control disorders?

Back 32

ropinirole and pramipexole

Front 33

Syncope or hypotension can occur in early treatment of ropinorole or pramipexole?

Back 33

ropinorole

Front 34

What can cause sudden onset of sleep with no warning?

Back 34

Pramipexole

Front 35

Used as initial therapy (without l-dopa) or as adjunctive therapy with l-dopa

Back 35

Ropinirole or Pramipexole (D agonists)

Front 36

What is an ergot compounds which possess dopaminergic activity?

Back 36

Bromocryptine

Front 37

What drug acts by direct stimulation of dopamine RECEPTOR?

Back 37

bromocryptine:

rapidly absorbed, effective levels reached quickly and persists 3 4 times longer than 1 dopa

Front 38

injectable, non-ergot DA agonist approved for INTERMITTENT, SubQ treatment of “off” episodes – a “rescue” treatment. Adverse effects include vomiting, orthostatic hypotension and syncope.

Back 38

Apomorphine

Front 39

What is an antiviral agent found to be effective against PD?

Back 39

Amantadine

Front 40

MoA of Amantaide?

Back 40

Apparently acts by increasing dopamine release from intact dopaminergic neurons. Also blocks NMDA (glutamate) receptors.

Front 41

What drug is effective quickly but for SHORT time (6 8 weeks). Also used to control DYSKINESIAS occurring with l-dopa therapy late in progression of disease.

Back 41

Amantadine

Front 42

May cause livedo reticularis (a condition of the peripheral blood vessels characterized by reddish blue mottling of the skin especially of the extremities usually upon exposure to cold)

Back 42

Amantadine

Front 43

What anticholingergies are used as adjunt to 1-dopa therapy?

Back 43

Trihexyphenidyl and Benztropine

Front 44

These agents block the unopposed cholinergic effects in the basal ganglia of PD patients

Back 44

Trihexphhenidyl and Benztropine

Front 45

Decreases tremor, LITTLE effect on rigidity and bradykinesia, may have some autonomic symptoms

Back 45

Trihexyphenidyl and Benzotrpine

Front 46

What drugs AR include confusion, cyclopelgia (paralysis of cilliary m --> no accomadation), constipation, urinary retention

Back 46

Trihexphenidyl and benzotropine

Front 47

What drug inhibits MAOB which decreases the catabolism of DA?

Back 47

Selegiline

Front 48

What's the difference between MAOA and MAOB?

Back 48

A: degrades 5HT and NE

B: degrades dompaine

Front 49

Decreases progression of Parkinsons Dz.

Back 49

Dopamine Agonists (Ropinirole and Pramipexole)