Antiparkinson and Cholinergic Drugs

what is Parkinson’s disease

• Progressive disease affecting 10 million people worldwide

• Can be idiopathic (most cases; unknown cause) or secondary (ex: medications & toxins - symptoms can improve or even go away when you stop taking the causative medication like dopamine receptor blockers or dopamine depleting agents)

• Progressive loss of dopamine producing neurons (symptoms appear when 50-80% are lost)

risk fx for parkinson’s

• Age: mostly after 50

• Gender: males more than females

• Genetics: 15-20%  have family history

• Environment: toxins (pesticides, herbicides, heavy metals, well water) and head injury possible triggers

dx for parkinsons

• Based on motor symptoms (tremor, rigidity - mask face, akinesia/bradykinesia, postural instability - shuffling walk): 2 of 4 symptoms

• Detailed medical history

• MRI will be normal and i used to exclude other causes.

• DAT scan can help differentiate it from other tremor disorders (not required)

• Medication response: very good response to levodopa/meds highly signals it was Parkinsons

goal of therapy for Parkinson meds

Slow progression (increase QOL) & control symptoms (motor & non-motor)

Highly individualized treatment

general assessment for drug tx for parkinson’s

• Baseline VS and swallowing ability (risk for aspiration)

• Baseline neurological, mental status, and motor function

common s/e for Parkinson meds

• CNS: dizziness, drowsiness, confusion, h/a, vivid dreams

• GI: n/v, dry mouth

• CV: orthostatic hypotension, palpitations

adverse effects for Parkinson meds in general

• Severe or worsening dyskinesia (head bobbing, facial grimacing, writhing movements)

• Hallucinations (psychosis, paranoias, severe confusion)

• Worsening symptoms 

• Difficulty swallowing or signs of aspiration

• Severe HOTN, syncope, angina, or dysrhythmias

pt teaching for Parkinson meds in general

• Fall prevention #1 - change position slowly, gradually increase activity, use assistive devices

• GI upset - Take medications with food, avoid high-protein meals around levodopa doses, drink lots of water & high fiber foods

• Daily living - Do not drive/do high risk activities until drug effects are known

• Medication adherence (take exactly as prescribed at regular intervals; if a dose is missed, take it right when you remember, unless your next dose in within 2 hours - never double up on doses)

• When to call provider (adverse effects; compulsive behaviors)

subcategories of Parkinson meds

• indirect acting dopaminergic drugs - MAOIs

• dopamine modulator

• COMT inhibitors

• direct-acting dopamine receptor agonists 

  • nondopamine-dopamine receptor agonists

  • dopamine replacement drugs

• anticholinergics

when are MAOIs given
dosing considerations

• Used in early stages (mild symptoms) to delay levodopa need, adjunct in later stage to reduce “off” periods (w/ levodopa)

• Dosing Considerations - Start low. Selegiline in AM and lunch (prevents insomnia).

MAOI examples

Selegiline (Oral, buccal, and transdermal; Twice daily) & Rasagiline (Oral, Once daily)

major interactions of MAOIs

• Meperidine, tramadol, methadone: serotonin syndrome

• SSRIs, SNRIs, TCAs, St. John's Wort: high risk of serotonin syndrome

• Tyramine rich foods (aged cheese, cured meats, pickled foods) and sympathomimetics: hypertensive crisis

• Other dopaminergic drugs like levodopa b/c increased side/adverse effects (weigh risks vs benefit)

s/e MAOIs

• N/V

• h/a

• dizziness

• lightheadedness

• insomnia (especially with Selegiline if taken later in afternoon/night)

• OH

adv effects MAOIs

• Hypertensive crisis - rare at therapeutic doses (possible at higher and non-selective doses) → n/v, chest pain, severe h/a, photophobia, dilated pupils, diaphoresis

  • don’t eat tyramine rich foods, increases risk

• Serotonin syndrome - agitation, hallucinations, delirium, coma, tachycardia, diaphoresis, flushing, tremor, rigidity, hyperreflexia, myoclonus/rhythmic spams, GI distress

  • don’t take with any other drugs that cause SS

• Neuropsychiatric events (hallucinations, agitation, confusion, & vivid dreams (especially with levodopa)

• Motor complications (worsening dyskinesias w/ levodopa)

Nursing Considerations/Patient Teaching MAOIs

• Monitor BP and HR (HOTN or HTN crisis)

• Assess improvement or worsening motor function

• Medication teaching - Don’t double dose, don’t stop medication abruptly, report any severe h/a, palpitations, chest pain, hallucinations, or uncontrolled movements immediately

• Avoid OTC cold medicines, decongestants, or stimulants without HCP approval, maintain a consistent dosing schedule

• Safety

• Dietary teaching - Caution with very high tyramine containing foods & limit excessive caffein to reduce jitteriness and insomnia 

dopamine modulator example
when is it used?

Amantadine

Used early stages (mild Parkinson s/s), in advanced stages it is used as adjunct therapy. Good for muscle symptoms like tremors/dyskinesia 

dosing considerations amantadine

• Immediate release: 3x/day

• Extended release: daily

• Renal adjustment required (impaired kidney function)

• Start low - especially with older adults

• Pediatrics - rarely used because the safety is not well established

major interactions of amantadine

• Anticholinergics: additive effect (increased risk for confusion, urinary retention, blurred vision, dry mouth, constipation)

• Antihistamine, antipsychotics, and alcohol leads to increase in confusion, hallucinations, or sedation

• Diuretics (HTZ) - can reduce renal clearance of amantadine (leading to toxicity)

s/e of amantadine

• CNS: insomnia, dizziness, lightheadedness

• GI: n/v, loss of appetite/anorexia, constipation

• Other: dry mouth, peripheral edema

adv effects of amantadine

dopamine modulator

• Hallucinations, confusion, agitation, psychosis (elderly or higher doses more common)

• Orthostatic hypotension

• Livedo reticularis - purple, mottled, net-like skin discoloration (reversible)

• Seizures (very rare)

• Renal toxicity - severe confusion, agitation, or myoclonus if the dose is not adjusted in renal impairment PTs

RN consid/pt teaching amantadine

• Monitor BP, renal function, skin changes 

• Assess fall risk (teach safety)

• Take as prescribed, do not double dose, do not abruptly stop medication

• When and what to report to provider

• Maintain hydration to reduce dizziness and constipation

• Avoid alcohol & CNS depressants unless they’re approved by provider

• Take it earlier in the day if they have insomnia

main aspect of COMT inhibitors

Only effective when used in combination with Levodopa; adjunct therapy w/ levodopa or carvedopa for those with motor fluctuations/”off periods”.

Not monotherapy.

COMT inhibitor meds

Entacapone (shorter acting) & Tolcapone (longer acting & high hepatotoxicity risk)

COMT inhibitors dosing considerations

• Give with levodopa - ALWAYS combination therapy

• Baseline and ongoing LFT monitoring (tolcapone - high hepatotoxicity risk)

• May need titrated

• Swallow tablets whole

major interactions of COMT inhibitors

• Levodopa/Carbidopa: increased side effects

• Talcapone with other hepatotoxic drugs/drugs metabolized in liver (LFTs)

• Nonselective MAOIs: risk of hypertensive crisis

• Warfarin: entacapone increases bleeding risk (increases INR)

• Other CNS depressants/alc: increased drowsiness and confusion

s/e of COMT inhibitors

entecapone & talcapone

• GI upset

• Dyskinesia (due to increased levodopa availability)

• Urine discoloration - orange/brown

• less commonly - Fatigue, OH, dizzy

adv effects of COMT inhibitors

• Neuroleptic malignant syndrome (NMS)

- triggered by sudden withdrawal/reduction of medication (s/s are high fever, lead pipe rigidity, unstable vitals/fluctuating, altered mental status, autonomic instability, rhabdomyolysis → if untx can lead to AKI)

• Hepatoxicity

RN consid/pt teaching COMT inhibitors

• Never used alone

• Monitor for adverse effects (get baseline LFTs and check often - jaundice, abd pain, dark urine, nausea/fatigue)

• Educate patient on what to report immediately

• Expect urine discoloration

• Take doses consistently 

indications of nondopamine dopamine receptor agonists

Monotherapy in early disease, adjunct therapy w/ Levodopa to reduce “off periods”

subclasses of nondopamine dopamine receptor agonists

• Ergot Derivative (increased risk of fibrosis and CV complication) - Bromcocriptine

• Non-ergot Derivative (preferred; fewer CV and fibrotic risks)  - Pramipexole, Ropinirole, Rotigotine

dosing considerations nondopamine dopamine receptor agonists

Start low, titrate slow to minimize s/e

major interactions of nondopamine dopamine receptor agonists

• Alcohol and CNS Depressants: additive sedation and drowsiness

• Antihypertensives: increase risk of orthostatic hypotension

• CYP1A2 inhibitors (Ciprofloxacin): may increase ropinirole levels

s/e of nondopamine dopamine receptor agonists

nonergot & ergot derivatives

• N/V

• Orthostatic hypotension

• Daytime sleepiness or insomnia

• Fatigue

• Constipation

• Peripheral edema

• Impulse control disorders (pathologic gambling, impulsive shopping, binge eating, hypersexual)

adv effects of nondopamine dopamine receptor agonists

• Severe hypotension/syncope

• Hallucinations, severe confusion, psychosis

• Pulmonary, retroperitoneal, and cardiac fibrosis

• Sudden sleep attacks

RN consid/pt teaching nondopamine dopamine receptor agonists

• Monitor BP and risk for falls, rise slowly

• Assess mental status

• Educate patient about sleep attacks; use caution when driving

• Gradual dose titration; do not stop abruptly; take as prescribed

• Caregivers should monitor for behavior changes. Report any s/s

• Avoid alcohol and CNS depressants

indications of Dopamine Replacement Drugs

• Moderate to severe Parkinson’s to improve bradykinesias

• Improves “off” period fluctuations

med examples of Dopamine Replacement Drugs

• levodopa

• carbidopa

dosing considerations Dopamine Replacement Drugs

• Immediate release: TID and titrate slowly (based on response and tolerability)

• Controlled release: more consistent plasma levels and help reduce wearing-off effects

• Timing: avoid doses around high-protein meals (reduce absorption)

major interactions of Dopamine Replacement Drugs

• Nonselective MAO inhibitors: Hypertensive crisis

• Dopamine agonists, MAO-B inhibitors, COMT inhibitors: additive effects (increased risk for dyskinesias, HOTN)

• Protein-rich meals: decrease absorption of levodopa

s/e of Dopamine Replacement Drugs

• CNS: dizziness, headache, insomnia, somnulence

• CV: orthostatic hypotension, palpitations

• GI: n/v, anorexia

• Musculoskeletal: dyskinesias

• Other: Dark body fluids (urine/sweat can turn brown - harmless)

adv effects Dopamine Replacement Drugs

• CNS: Hallucinations

• CV: arrhythmias, syncope

• Motor: uncontrolled dyskinesias

• Other: Parkinson’s Crisis (if drug is stopped abruptly)

RN consid/pt teaching of Dopamine Replacement Drugs

• Monitor orthostatic BP and fall risk; rise slowly

• Assess mental status, motor function and psych changes or changes in behavior

• Encourage consistent timing; same time each day; do not stop abruptly

• Avoid high protein meals with dosing

• Educate about dark body fluids with meds

what are anticholinergics

oldest classes of PD drugs - usually used in beginning of Parkinson's for early tremors (limited effect)

anticholinergic drugs ex

• Benztropine: once daily

• Trihexyphenidyl: TID

dosing considerations anticholinergics

• Start low

• Use in caution with elderly

• Titrate gradually (monitor for anticholinergic effects)

• Renal and hepatic patients may require a dose reduction 

drug interactions of anticholinergics

• Antihistamines and antipsychotics: additive effect (dry s/s increase)

• Alcohol or CNS depressants: increased sedation

• Other anticholinergics: risk of paralytic ileus, urinary retention, and heat stroke

• Glaucoma medications: can worsen intraocular pressure

s/e anticholinergics

• Dry mouth

• Constipation

• Blurred vision

• Decreased sweating

• Urinary retention

adv effects anticholinergics

• Worsening glaucoma

• Heatstroke

• Bowel obstruction or severe constipation

RN consid/pt teaching anticholinergics

• Assess vision; Regular vision exams

• Assess bowel function daily; bowel care

• Rinse mouth frequently (gum, saliva substitutes), good oral hygiene

• Safety in hot weather - avoid prolonged heat exposure, hydrate

• When to notify provider 

what are the two types of cholinergic drugs & examples

• direct-acting

  • Bethanechol:  specifically targets bladder and GI tract

  • Pilocarpine: specifically targets eye to reduce intraocular pressure

• indirect-acting

  • Donepezil, Rivastigmine: enhancement in Alzheimer's

  • Pyridostigmine: improve neuromuscular transmission in myasthenia gravis

dosing considerations cholinergic drugs

• Do not adjust dose without provider approval

• Specific drugs safe for pediatrics: Bethanechol and Pyridostigmine

• Monitor hypotension, dizziness, and respiratory issues closely in older adults

major interactions of cholinergic drugs in general

• Anticholinergics: antagonize effects (decreases effectiveness of these drugs)

• Other cholinergic drugs: additive effect

• Beta Blockers: additive CV effects

• Neuromuscular Blockers: prolonged effects (with cholinesterase inhibitors)

what should you assess prior to giving cholinergic drugs

GI, GU, and cardiac conditions prior to therapy for all age groups

expected effects of cholinergic drugs in general

• GI/GU: increased effects (gastric secretion and motility, increased frequency)

• Ocular: decreased intraocular pressure (by pupillary constriction)

• CV: Decreased effects (increased salivation and sweating, decreased HR, vasodilation)

• Resp: Bronchial constriction

general s/e cholinergic drugs

• GI: n/v/diarrhea

• Salivary: increased effects/sweating

• GU: urgency

• Other: headache, flushing, dizziness

adv effects cholinergic drugs in general

• Toxicity (Cholinergic Crisis)

• Severe CV symptoms

• Resp distress

• Excessive secretions (increase risk for aspiration)

• Seizures (rare, with overdoses)

• SLUDGE

what is SLUDGE for cholinergic crisis

• Salivation

• lacrimation

• urination

• diarrhea

• GI cramping

• emesis

what is antidote for cholinergic crisis

Atropine - should be kept at bedside and immediately available for patients that take these medications

RN consid/pt teaching for cholinergic drugs

• Monitor VS, resp status, I&O, fall risk; rise slowly

• Give IV slowly to prevent cardiac arrest

• Give oral doses 30m before meals for myasthenia gravis for swallowing/chewing

• Watch for/Teach signs of Cholinergic Crisis

• Carry medical ID 

• Do not stop abruptly

what are example meds of direct-acting cholinergic drugs

• bethanechol

• carbachol

• cevimeline

• succinylcholine

what is bethanechol used for

increase bladder tone and motility while relaxing sphincters (post-op/partum urinary retention)

s/e of bethanechol

hypotension, bradycardia, abdominal cramps, n/v, headache, increased salivation

adv effects of bethanechol

Cholinergic Crisis, bronchospasm, heart block/syncope

nursing administration for bethanechol

Give on empty stomach, monitor urinary output, blood pressure, and heart rate for cholinergic crisis

drug interactions for bethanechol

Decreased effectiveness with anticholinergics, increased toxicity with other cholinergics, and added bradycardia and HOTN with beta-blockers

what is carbachol used for

glaucoma and intraocular surgeriess (used topically - reduces intraocular pressure by miosis)

s/e carbachol

Ocular irritation, headache, sweating, potential bradycardia and HOTN if absorbed systemically

nursing admin for carbachol

Monitor intraocular pressure and teach patient proper instillation techniques

drug interactions for carbachol

Additive effects when used with other ocular HOTN drugs

what is cevimeline used for

stim salivary gland secretion (for sjogren syndrome)

s/e cevimeline

sweating, nausea, rhinitis, diarrhea, visual disturbances

adv effect cevimeline

bradycardia, hypotension, bronchospasm

nursing admin for cevimeline

Monitor swallowing ability, hydration status, and vision

drug interactions for cevimeline

Beta blockers can increase bradycardia and anticholinergics may antagonize effect

what is succinylcholine used for 

depolarizing neuromuscular blocker (adjunct to general anesthesia for intubation)

s/e succinylcholine

muscle fasciculations (temporary paralysis - only used in control setting with ventilatory support available - supreme caution), post-op muscle pain

adv effect succinylcholine

malignant hyperthermia, prolonged apnea, cardiac arrest, hyperkalemia

nursing admin for succinylcholine

Closely monitor potassium, HR, and RR

drug interactions for succinylcholine

Additive neuromuscular blockades with aminoglycosides and other neuromuscular blockers. 

meds of indirect-acting cholinergic drugs

• donepezil

• memantine

what is donepezil used for

mild to mod Alz disease

s/e donepezil

GI symptoms, increased salivation, muscle cramps, bradycardia, HOTN, bronchoconstriction

adv effect donepezil

Cholinergic Crisis, seizures, bronchospasm, cardiac arrest, insomnia

nursing admin donepezil

Monitor v/s, RR, and urinary output

Administer at bedtime to reduce GI upset.

Take medication with food if it causes with GI upset.

Therapeutic effects may take weeks to kick in.

Report black or tarry stools. 

drug interactions donepezil

Reduced effectiveness with anticholinergics, increased toxicity with other cholinergic agents, additive bradycardia with beta blockers, and prolonged effects with neuromuscular blockers

what is memantine used for

mod to severe alz disease

s/e memantine

headache, dizziness, GI symptoms, fatigue, occasional muscle discomfort

adv effect memantine

hypotension, pronounced ataxia

nursing considerations & interactions memantine

Monitor BP, mental status, and affect for fall risk.

Additive CNS toxicity hen combined with other NMDA antagonist (significant dizziness → falls and serious CNS effects) and reduced renal clearance with alkalizing agents