Antiparkinsons

Question 1

Parkinson’s Disease

Answer 1

Affects dopamine producing neurons in the brain

Symptoms caused by imbalance of dopamine and acetylcholine

Most drugs focus on DA pathway
as long as there are functioning nerve terminals, symptoms can be partially controlled

Question 2

Dopamine System Drugs

Answer 2

Indirect:
Levodopa-carbidopa

Entacapone

Selegiline

Amantadine

Indirect:
Benztropine (anticholinergic)

Question 3

Levodopa Therapy

Answer 3

Indirectly affects DA

Levodopa is a precursor of dopamine

Blood-brain barrier does not allow exogenously supplied dopamine to enter, but does allow levodopa which is taken up by dopaminergic terminal and converted into dopamine

Aimed at increasing dopamine release from **surviving* DA neurones

Eventually levodopa fails to control PD and pt becomes debilitated around 5-10 yrs later

Question 4

Levodopa Combination Therapy

Answer 4

Carbidopa given with levodopa

Carbidopa does NOT cross the blood-brain barrier. BUT it *prevents levodopa breakdown** in the periphery.

Levodopa can also be metabolized to inactive substance by enzyme COMT. Thus, use COMT inhibitors

Question 5

COMT Inhibitors

Answer 5

Levodopa can be metabolized into inactive substance by the enzyme COMT

So we COMT inhibitors:
DRUG: Entacapone
Inhibits COMT so more levodopa is available to enter brain

Question 6

Combination Therapies Drugs Examples

Answer 6

Levodopa + Carbidopa
OR
Levodopa + Carbidopa + Entacapone

Question 7

Levodopa Adverse Effects

Answer 7

Dyskinesia (involuntary muscle movements)

Question 8

Other Indirect Dopaminergic Therapies

Answer 8

Selegiline
-Irreversible MAOI that selectively inhibits MAO-B
-Inhibits DA breakdown in neurons
-Does not elicit the “cheese effect” of nonselective MAOIs

Amantadine
Causes release of dopamine from storage sites at end of nerve cells that are still intact.
Also blocks reuptake of dopamine into nerve endings.
May help with levodopa induced dyskinesia

Question 9

Selective MAO-B Therapy (Selegiline) Indications

Answer 9

Used for milder symptoms earlier in disease

Used in combination with levodopa or levodopa-carbidopa

Adjunctive agent when response to levodopa is fluctuating

Question 10

Direct acting dopaminergic therapy

Answer 10

-DA receptor agonists
-No conversion required, no dietary restrictions, less dyskinesia
-1st line Tx for younger patients with mild/moderate symptoms
-Less effective than levodopa

Risk or hallucinations, postural hypotension, impulse control disorders.

Assist client with walking because of dizziness

Question 11

Levodopa Client Implications

Answer 11

Avoid high protein diets. Amino acids reduce GI absorption

Non-selective MAOIs with Levodopa can cause hypertensive crisis

Levodopa may darken urine and sweat

Question 12

Anticholinergic Agents

Answer 12

Greater influence of cholinergic excitatory pathways on muscle control

-Muscle tremors
-Cogwheel rigidity
-Pinrolling movement of fingers and head bobbing at rest

-Anticholinergics block effects of ACh
-Used to treat muscle tremors and rigidity associated with PD
-Drugs DO NOT relieve bradykinesia (slow movements)

Question 13

Anticholinergic Drugs

Answer 13

Benztropine

Question 14

Other anticholinergic indications

Answer 14

Also used to treat drug-induced extrapyramidal symptoms (EPS)

Question 15

Anticholinergic Adverse Effects and client care implications

Answer 15

ADVERSE:
Drowsiness, confusion
Constipation, nausea, vomiting
Urinary retention,
Blurred vision, dilated pupils
Dry mouth

Care Implications:
-Assess for s&s of PD: masklike expression, dysphagia
-Monitor for response to drug therapy (improved mental status, appetite, ability to perform ADLs