• Parkinsonism includes tremors, rigidity, slow movement (bradykinesia), slurred speech, maskface, difficulty chewing/swallowing; unsteady gait with upper body bent forward
• Other conditions beside Parkinson’s disease can cause, though PD most common
• Drug adverse reactions can cuase parkinsonism reactions = extrapyramidal symptoms

levodopa

levodopa with carbidopa

 amantadine

 bromocriptine

rasaglinine 

selegiline

dopaminergic drugs (increase dopamine in CNS)

rasaglinine and selegiline are MAOI dopaminergics (dopamine agonists)

a.        Increase dopamine (Parkinson's decrease in dopamine)

b.       Only crosses B-B Barrier in small amounts

c.        Carbidopa is only used with levodopa to increase levodopa absorption (no affect on own carbidopa)

d.       levodopa is converted into dopamine

e.        others work various mechanisms

dopamine receptor agonists (other)

taken transdermally, not oral

a.        parkinson's

b.       Extrapyramidal symptoms (parkinson's like)

c.        Restless leg syndrome

d.       viral infections

• levodapa/carbidopa effect decreases over time
• dry mouth, difficulty swallowing
• ab pain constipation
• increased hand tremor
• headache and dizziness
• Most serious with levodapa are CHOREIFORM MOVEMENTS
• Less common are mental changes like dementia, depression, psychotic episodes, paranoia, suicidal tendencies

•   invol twitching of limbs or facial muscles, dystonic movements (spasms of tongue, jaw, eyes, neck usually)
• can be caused by levodopa/carbidopa admin
• If occurs, withhold and notify immediately

                                                               i.      narrow-angle glaucoma

                                                              ii.      MAOIs

                                                            iii.      can activate malignant melanoma

                                                               i.      opioid meperidine (Demerol) bc of antimetabolite conversion

• CV or pulm disease
• peptic ulcers
• renal or hepatic disease
• psychosis
•  pregnancy and lactation (cat C)

1.        benztropine

2.        biperiden

3.        diphenhydramine

4.        procyclidine

5.        trihexyphenidyl

• cholinergic blocking (anticholinergic) drugs for treatment of parkinsonism 
• are used for other conditions as well

1. ACh is increased in Parkinson's, so drugs are used to block this to enhance dopamine transmission
2. less effective than levodopa
3. dosage limited by adverse reactions - diphenhydramine has least effects, best for elderly

1. adjunct to all forms of parkinsonism
2. control drug induced extrapyramidal effects

1. dry mouth
2. blurred vision
3. dizziness
4. mild nausea
5. nervousness
6. rash, urticaria
7. urinary retention, dysuria
8. tachycardia
9. muscle weakness
10. disorientation, confusion
11. >60 often have sensitivity to anticholinergics, require close monitor, esp. confusion and disorientation; may need lower doses

1. angle-closure glaucoma
2. pyloric or duodenal obstruction
3. peptic ulcers
4. prostate hypertrophy
5. achalasia (difficulty swallowing from lower esoph. muscles not relaxing)
6. myesthenia gravis
7. megacolon

1. tachydardia
2. cardiac arrhythmias
3. hyper/hypo tension
4. tendency towards urinary retention
5. decreased liver or kidney function
6. obstructive disease of GI tract
7. older adults

Remember that anticholinergics are drying, which can reduce blood volume.  This can increase heart rate to compensate.  Therefore, caution with existing tachycardia, arrythmias, BP issues, inability to pee, kidneys/liver preexisting problem and need blood flow, GI stasis

AND OLDER ADULTS MORE SENSATIVE TO ALL

1.        entacapone

2.        tolcapone

1. prolong effect of levodopa by bloching the enzyme COMT (normally eliminates dopamine)
2. increase plasma concentration and duration of action levodopa

1. adjunct to levodopa/carbidopa for Parkinson's
2. Tolcapone reserves for those not responding to other treatments bc very hepatotoxic
3. Entacapone less stong than tolcapone

1. dizziness
2. dyskinesias, hyperkinesias
3. nausea, anorexia, diarrhea
4. orth hypo
5. sleep disoreders, excessive dreaming, somnolence
6. muscle cramps
7. liver failure and death with tolcapone

1. pregnancy and lactation (cat C)
2. Tolcapone contra in those with liver dysfunction

1. hyper/hypo tension
2. decreased renal and hepatic function (except tolcapone contraindication liver dysfunction)

1.        apomorphine

2.        pramipexole

3.        ropinirole

• Non-ergot dopamine receptor agonists
• Not derived from ergot, which is a fungus
• Early dopamine agonists were ergot-derived (are not included in book)

1. not understood
2. thought to act on postsynaptic dopamine receptors in brain, mimicking effect of dopamine

1. Parkinson's
2. apomorphine is used for "on-off" phenomenon and must be given with an antiemetic

• pramipexole and ropinirole (apomorphine not included)
• N/V, dizziness
• Insomnia
• somnolence, hallucinations, confusion, visual disturbances
• postural hypotension
• abnormal involuntary movements
•  headache
• dyspepsia

1. safety not established for pregnancy (cat C)

1. dyskinesia
2. ortho hypo
3. hepatic or renal impairment
4. CV disease
5. hx hallucinations or psychosis

a.        Hx may be hard to obtain from Parkinson pt bc of mental changes; may question family member, etc

b.       Assess symptoms, how long sxs, ADL ability, mental condition (memory, depression, withdrawal, etc.)

c.        Physical assessment for baseline

d.       Eval neuromuscular status, e.g. tremors, mask-face, gait, speech, etc

a.        Observe neuromuscular status to evaluate response t odrug

b.       Improvement may be slow

a.        Optimal response requires adjustments/titration, explain this to pt and family; Report all adverse reactions to help with dosage adjustments

a.        When given to manages adverse reactions to other drugs, antiparkinsonism drugs may worsen mental sxs leading to psychotic event – observe pt’s behavior frequently – if sudden behavioral change, withhold and immediately notify PCP

•   NURSING ALERT – tolcapone (Tasmar) can cause fatal hepatotoxicity.
• Usually prescribed regular hepatic fnx tests including serum aminotransferase q 2 weeks for first year, and q 8 weeks afterwards. 
• Tx DC if aminotransferase is high OR S/S of hepatic failure:
• observe for persistent nausea, fatigue/lethargy, anorexia, jaundice, dark urine, pruritus and RUQ tenderness.

a.        for carbidopa/levodopa admin, watch for CHOREIFORM and dystonic movements such as facial grimacing, protruding tongue, exaggerated chewing, jerking of extremities.  If these occur, withhold dose and immediately notify PCP bc drug may need reduction of DC.

• ON-OFF PHENOMENON can occur with LEVODOPA.  
• Sudden change from improvement to loss of tx effect.
•  Associated with long term levodopa use. 
• Sometimes, PCP orders a “drug holiday,” where pt is completely w/drawn from levodopa for 5-14 days and gradually restarted at lower dose
• Must monitor for COMPLICATIONS OF LEVODOPA WITHDRAWAL, which can be severe

a.        AbruptDC of antiparkinsonism drugs is bad.  Can cause a “neuroleptic malignant-like syndrome,” including (watch for) muscle rigidity, high temp, mental changes.

Re: antiparkinsonism drug admin:

“Imbalanced Nutrition: Less Than Body Requirements rt nausea, dry mouth"

a.        Help with dry mouth by suggesting sipping water, ice, hard candy if allowed. 

b.       If very severe dry mouth w/ difficulty swallowing or speaking, or if loss of appetite, dosage may need reduction (so report to PCP)

c.        Some have N/V and/or constipation which can affect nutrition.  So, small frequent meals, caml environment, and serve preferred food to help eat.  Also weigh daily.  Sometimes helped by giving med with food.

d.       Severe N/V may require DC or changing drug, although nausea usually decreases or resolves over time

Re: antiparkinsonism drug admin:

 “Risk for Injury rt dizziness, lightheadedness, orthostatic hypotension, loss of balance”

a.        Parkinson’s alone caused problems with ambulation; with drugs can exacerbate:

b.       Antipark. drugs may cause blurry vision and diplopia (double vision)

c.        Report evidence of visual disturbance to PCP (pt may not verbalize problem)

d.       Also watch for sudden behavioral changes and report – hallucinations, depression, psychotic episodes

e.        Hallucinations more common with elderly taking antipark. drugs, esp. dopamine receptor agonists.  Assess older adults for hallucinations

f.         Adverse reactions of dizziness, muscle weakness and ataxia can worsen ambulation difficulty

g.       Parkinson pts prone to falls, good to help ambulate and encourage assistive devices like cane or walker, gripping shoes, good lighting, no throw rugs – carefully assess environment for obstacles, etc.

h.       Ortho hyp may result from drug tx – instruct accordingly (rise slowly, etc)

a.        evaluate pt’s understanding regimen, self-care ability, ability to comply.  If needs assistance, refer to social worker.

b.       Home environment should be set up to reduce likelihood of falling, e.g no throw rugs, hand rails,etc.

c.        For GI upset, take with food.

d.       Avoid hazardous tasks w/ dizziness, drowsiness, vision problems, etc

e.        Avoid alcohol unless approved

f.         If dry mouth interferes with dentures, consult dentist

g.       Ortho hypo teaching

h.       Dry mouth teaching

i.         When to notify PCP

                                                               i.      severe dry mouth

                                                              ii.      inability to chew or swallow

                                                            iii.      can’t urinate

                                                            iv.      depression, mood alterations

                                                             v.      severe dizziness

                                                            vi.      rapid or irregular heartbeat

                                                          vii.      ab pain

                                                         viii.      unusual movements

                                                             ix.      For levodopa, avoid B6 (pyridoxine) bc can interfere with action

                                                              x.      For diabetics taking levodopa, levodopa can cause inaccurate glucose and ketone testing, first report abnormal result to PCP (don’t alter doses of antidiabetic)

j.         For talcapone, especially important to keep appointments to test liver frequently; report any signs of liver failure, including persistent nausea, fatigue/lethargy, anorexia, jaundice, dark urine, pruritus and RUQ tenderness.

COMT inhibitor portion is entacapone, precautions are:

1. tachydardia
2. cardiac arrhythmias
3. hyper/hypo tension
4. tendency towards urinary retention
5. decreased liver or kidney function
6. obstructive disease of GI tract
7. older adults

Carbidopa has no effect alone

It is given with levodopa to increase amount of levodopa that reaches the brain

Levodopa alone doesn't cross BB barrier easily, and stays in periphery with adverse reactions

Carbidopa helps levodopa get to brain, therefore reducing dose of levodopa

plant and animal derived

converted into dopamine in body

only small amount cross BB barrier (carbidopa increases this)

ACHALASIA

With drug is contraindicated with this condition?

• difficulty swallowing from lower esoph. muscles not relaxing
• anticholinergics are contraindicated in those with achalasia

•  for carbidopa/levodopa admin, watch for CHOREIFORM and dystonic movements such as facial grimacing, protruding tongue, exaggerated chewing, jerking of extremities.  If these occur, withhold dose and immediately notify PCP bc drug may need reduction of DC.
• ABNORMAL MOVEMENTS

a.        Sometimes, PCP orders a “drug holiday,” where pt is completely w/drawn from levodopa for 5-14 days and gradually restarted at lower dose – MUST MONITOR FOR COMPLICATIONS:

b.       NURSING ALERT – AbruptDC of antiparkinsonism drugs is bad.  Can cause a “neuroleptic malignant-like syndrome,” including (watch for) muscle rigidity, high temp, mental changes.

apomorphine (Apokyn)

a dopamine receptor agonist

pyridoxine (B6) decreases effect of levodopa

Does not effect ACTION of levodopa if given with carbidopa)

B6 sometimes prescribed to lessen adv rxns (not action?) of levodopa

more sensitive to anticholinergics

carefully monitor

more confusion and disorientation

may need lower doses

Elderly more prone to hallucinations with antipark drugs

Especially with dopamine receptor agonists

levodopa only crosses in small amounts

carbidopa helps more cross BB barrier

• catechol-O-methyl transferase
• An enzyme involved in NT degradation
• For parkinson's, prevents breakdown of dopamine

AMANTADINE

What type of drug is it?

BROMOCRIPTINE

What kind of drug and what used for?

RASAGILINE

SELEGILINE

What class of drugs are these?

slurred speech

ataxia

lethargy

dizziness

N/V

non-ergot dopamine receptor agonist

Used to contol on-off syndrome

q 2 weeks first year

q 8 weeks afterwards

For on-off phenom of levodopa in parkinson's

Must be given with an anti-emetic

• severe dry mouth
•  inability to chew or swallow
•  can’t urinate
• depression, mood alterations
• severe dizziness
• rapid or irregular heartbeat
• ab pain
• unusual movements